PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 30224050-1 2018 Point mutations in p21ras are associated with ~30% of human tumors by disrupting its GTP hydrolysis cycle, which is critical to its molecular switch function in cellular signaling pathways. Guanosine Triphosphate 85-88 HRas proto-oncogene, GTPase Homo sapiens 19-25 30991803-1 2019 p21ras protein activity, regulated by GTP hydrolysis, constitutes an active field of research for the development of cancer targeted therapies that would concern ~30% of human tumors to which specific mutations have been associated. Guanosine Triphosphate 38-41 HRas proto-oncogene, GTPase Homo sapiens 0-6 30367521-1 2019 H-Ras oncogene plays a critical role in the transformation of normal cells to a malignant phenotype through constitutive activation of the GTP bound protein leading to uncontrolled cell proliferation in several human cancers. Guanosine Triphosphate 139-142 HRas proto-oncogene, GTPase Homo sapiens 0-5 30339365-0 2018 Quantitative Measurement of Intrinsic GTP Hydrolysis for Carcinogenic Glutamine 61 Mutants in H-Ras. Guanosine Triphosphate 38-41 HRas proto-oncogene, GTPase Homo sapiens 94-99 30141910-0 2018 Molecular Basis for Allosteric Inhibition of GTP-Bound H-Ras Protein by a Small-Molecule Compound Carrying a Naphthalene Ring. Guanosine Triphosphate 45-48 HRas proto-oncogene, GTPase Homo sapiens 55-60 30141910-3 2018 Here, we report the discovery of a small-molecule compound carrying a naphthalene ring, named KBFM123, which binds to the GTP-bound form of H-Ras. Guanosine Triphosphate 122-125 HRas proto-oncogene, GTPase Homo sapiens 140-145 27865780-2 2017 Here, we design genetically encoded antibody-like ligands (intrabodies) that recognize active, GTP-bound K- and H-Ras. Guanosine Triphosphate 95-98 HRas proto-oncogene, GTPase Homo sapiens 112-117 29719614-5 2018 The signal inhibition occurred at the level of H-Ras, as it showed impaired GDP-to-GTP exchange and further interaction with its effector molecule, Raf. Guanosine Triphosphate 83-86 HRas proto-oncogene, GTPase Homo sapiens 47-52 28837923-0 2017 Structural transition of solvated H-Ras/GTP revealed by molecular dynamics simulation and local network entropy. Guanosine Triphosphate 40-43 HRas proto-oncogene, GTPase Homo sapiens 34-39 28837923-1 2017 The state transitions of solvated H-Ras protein with GTP were theoretically analyzed through molecular dynamics (MD) simulations. Guanosine Triphosphate 53-56 HRas proto-oncogene, GTPase Homo sapiens 34-39 29235861-5 2018 This open conformation is consistent with the inactive "state 1" previously observed for HRAS bound to GTP. Guanosine Triphosphate 103-106 HRas proto-oncogene, GTPase Homo sapiens 89-93 29750207-3 2017 The conventional GTPase mechanism such as in H-Ras requires a conserved glutamine (Q64) in the switch-II region of RheB to align the catalytic water molecule for efficient GTP hydrolysis. Guanosine Triphosphate 17-20 HRas proto-oncogene, GTPase Homo sapiens 45-50 27865780-4 2017 Primary selection of ligands against Ras with mRNA display resulted in an intrabody (termed RasIn1) that binds with a KD of 2.1muM to H-Ras(G12V) (GTP), excellent state selectivity, and remarkable specificity for K- and H-Ras. Guanosine Triphosphate 147-150 HRas proto-oncogene, GTPase Homo sapiens 220-225 27820802-4 2017 We developed NS1, a synthetic binding protein (monobody) that bound with high affinity to both GTP- and GDP-bound states of H-RAS and K-RAS but not N-RAS. Guanosine Triphosphate 95-98 HRas proto-oncogene, GTPase Homo sapiens 124-129 28002430-8 2016 Consistently, functional characterization in vitro confirmed elevated HRAS-GTP accumulation and downstream RAS-MAPK pathway activation that are known to drive cell proliferation in LVH. Guanosine Triphosphate 75-78 HRas proto-oncogene, GTPase Homo sapiens 70-74 25846136-4 2015 In this study, we provide a comprehensive comparison of the dynamics of all the three RAS isoforms (HRAS, KRAS, and NRAS) using extensive molecular dynamics simulations in both the GDP- (total of 3.06 mus) and GTP-bound (total of 2.4 mus) states. Guanosine Triphosphate 210-213 HRas proto-oncogene, GTPase Homo sapiens 100-104 27412770-6 2016 The weak transient interaction between Sos and the second H-Ras GTPgammaS may provide a necessary mechanism for complex dissociation upon the completion of the native GDP GTP exchange reaction, but also explains measurable GTP GTP exchange activity of Sos routinely observed in in vitro assays that use fluorescently-labelled analogs of GTP. Guanosine Triphosphate 64-67 HRas proto-oncogene, GTPase Homo sapiens 58-63 27412770-6 2016 The weak transient interaction between Sos and the second H-Ras GTPgammaS may provide a necessary mechanism for complex dissociation upon the completion of the native GDP GTP exchange reaction, but also explains measurable GTP GTP exchange activity of Sos routinely observed in in vitro assays that use fluorescently-labelled analogs of GTP. Guanosine Triphosphate 173-176 HRas proto-oncogene, GTPase Homo sapiens 58-63 27057007-3 2016 In the present study, we model possible catalytic domain dimer interfaces of membrane-anchored GTP-bound K-Ras4B and H-Ras, and compare their conformations. Guanosine Triphosphate 95-98 HRas proto-oncogene, GTPase Homo sapiens 117-122 26888048-3 2016 To offer insights into the potential mechanism of patient mutation, protein structural analysis was performed using the resolved structure of human activated HRAS protein with bound GTP analogue (PDB id 5P21) in Discovery Studio 4.5 (Dassault Systemes Biovia, San Diego, CA). Guanosine Triphosphate 182-185 HRas proto-oncogene, GTPase Homo sapiens 158-162 26888048-5 2016 Our analysis suggests that the p.G12 mutations slow GTP hydrolysis rendering HRAS unresponsive to GTPase activating proteins, and resulting in permanently active state. Guanosine Triphosphate 52-55 HRas proto-oncogene, GTPase Homo sapiens 77-81 25935485-5 2015 Comparison with H-Ras and Rap2A reveals conservative mutations relative to Rap1B, distant from the bound nucleotide, which control how readily the protein may adopt the fully activated form in the presence of GTP. Guanosine Triphosphate 209-212 HRas proto-oncogene, GTPase Homo sapiens 16-21 25776558-3 2015 At the plasma membrane, H-Ras has been proposed to occupy distinct sublocations, depending on its activation status: lipid rafts/detergent-resistant membrane fractions when bound to GDP, diffusing to disordered membrane/soluble fractions in response to GTP loading. Guanosine Triphosphate 253-256 HRas proto-oncogene, GTPase Homo sapiens 24-29 25776558-6 2015 Interestingly, in both cases GTP loading results in H-Ras diffusing away from its original sublocalization. Guanosine Triphosphate 29-32 HRas proto-oncogene, GTPase Homo sapiens 52-57 27087647-3 2016 Intracellularly, Gal-1 was suggested to interact with the farnesylated C-terminus of Ras thus specifically stabilizing GTP-H-ras nanoscale signalling hubs in the membrane, termed nanoclusters. Guanosine Triphosphate 119-122 HRas proto-oncogene, GTPase Homo sapiens 123-128 27087647-11 2016 Our findings suggest stacked dimers of H-ras, Raf and Gal-1 as building blocks of GTP-H-ras-nanocluster at high Gal-1 levels. Guanosine Triphosphate 82-85 HRas proto-oncogene, GTPase Homo sapiens 39-44 27087647-11 2016 Our findings suggest stacked dimers of H-ras, Raf and Gal-1 as building blocks of GTP-H-ras-nanocluster at high Gal-1 levels. Guanosine Triphosphate 82-85 HRas proto-oncogene, GTPase Homo sapiens 86-91 25902334-1 2015 In many different human cancers, one of the HRAS, NRAS, or KRAS genes in the RAS family of small GTPases acquires an oncogenic mutation that renders the encoded protein constitutively GTP-bound and thereby active, which is well established to promote tumorigenesis. Guanosine Triphosphate 97-100 HRas proto-oncogene, GTPase Homo sapiens 44-48 29147425-1 2015 Background: Mammalian cells contain three functional RAS proto-oncogenes, known as H-RAS, K-RAS, and N-RAS, which encode small GTP-binding proteins in terms of p21rass. Guanosine Triphosphate 127-130 HRas proto-oncogene, GTPase Homo sapiens 83-88 23246410-1 2013 Oncogenic mutations in the small Ras GTPases KRas, HRas, and NRas render the proteins constitutively GTP bound and active, a state that promotes cancer. Guanosine Triphosphate 37-40 HRas proto-oncogene, GTPase Homo sapiens 51-55 25707436-9 2015 The method allows studying the GEF dependent H-Ras activation (GTP binding) and GAP-catalyzed H-Ras deactivation (GTP hydrolysis) at nanomolar protein concentrations. Guanosine Triphosphate 63-66 HRas proto-oncogene, GTPase Homo sapiens 45-50 24247240-5 2013 Here, we show that H-Ras is activated by monoubiquitination and that ubiquitination at Lys-117 accelerates intrinsic nucleotide exchange, thereby promoting GTP loading. Guanosine Triphosphate 156-159 HRas proto-oncogene, GTPase Homo sapiens 19-24 24224811-5 2013 This study established novel kinetic parameter-based equations that estimate the value of the cellular fractions of the GTP-bound active form of HRas mutant proteins. Guanosine Triphosphate 120-123 HRas proto-oncogene, GTPase Homo sapiens 145-149 24224811-7 2013 (i) The increase in the level of GTP-bound Ras is caused by the HRas mutation-mediated perturbation of the intrinsic kinetic characteristics of Ras. Guanosine Triphosphate 33-36 HRas proto-oncogene, GTPase Homo sapiens 64-68 24224811-8 2013 This generates a broad spectrum of the population of the GTP-bound form of HRas that typically causes Costello syndrome. Guanosine Triphosphate 57-60 HRas proto-oncogene, GTPase Homo sapiens 75-79 24224811-10 2013 (ii) The increase in the level of GTP-bound Ras occurs because the HRas mutations perturb the action of p120GAP on Ras. Guanosine Triphosphate 34-37 HRas proto-oncogene, GTPase Homo sapiens 67-71 24224811-11 2013 This causes production of a significantly high population of the only GTP-bound form of HRas linked merely to cancer formation. Guanosine Triphosphate 70-73 HRas proto-oncogene, GTPase Homo sapiens 88-92 25272152-1 2014 HRAS regulates cell growth promoting signaling processes by cycling between active (GTP-bound) and inactive (GDP-bound) states. Guanosine Triphosphate 84-87 HRas proto-oncogene, GTPase Homo sapiens 0-4 24884338-13 2014 H-rev107 is likely to suppress activation of the RAS signaling pathway by reducing the levels of palmitoylated H-RAS, which decreases the levels of GTP-bound H-RAS and also the activation of downstream molecules. Guanosine Triphosphate 148-151 HRas proto-oncogene, GTPase Homo sapiens 111-116 24884338-13 2014 H-rev107 is likely to suppress activation of the RAS signaling pathway by reducing the levels of palmitoylated H-RAS, which decreases the levels of GTP-bound H-RAS and also the activation of downstream molecules. Guanosine Triphosphate 148-151 HRas proto-oncogene, GTPase Homo sapiens 158-163 24309939-0 2013 Wentilactone A as a novel potential antitumor agent induces apoptosis and G2/M arrest of human lung carcinoma cells, and is mediated by HRas-GTP accumulation to excessively activate the Ras/Raf/ERK/p53-p21 pathway. Guanosine Triphosphate 141-144 HRas proto-oncogene, GTPase Homo sapiens 136-140 24309939-10 2013 Molecular docking analysis suggested that WA could bind to HRas-GTP, causing accumulation of Ras-GTP and excessive activation of Raf/ERK/p53-p21. Guanosine Triphosphate 64-67 HRas proto-oncogene, GTPase Homo sapiens 59-63 23967305-4 2013 Here, we report the crystal structure at 2.4-A resolution of the Grb14 RA and PH domains in complex with GTP-loaded H-Ras (G12V). Guanosine Triphosphate 105-108 HRas proto-oncogene, GTPase Homo sapiens 116-121 23630290-5 2013 The selected compound Kobe0065 and its analog Kobe2602 exhibit inhibitory activity toward H-Ras GTP-c-Raf-1 binding both in vivo and in vitro. Guanosine Triphosphate 96-99 HRas proto-oncogene, GTPase Homo sapiens 90-95 23630290-8 2013 The NMR structure of a complex of the compound with H-Ras GTP(T35S), exclusively adopting the unique conformation, confirms its insertion into one of the surface pockets and provides a molecular basis for binding inhibition toward multiple Ras GTP-interacting molecules. Guanosine Triphosphate 58-61 HRas proto-oncogene, GTPase Homo sapiens 52-57 23630290-8 2013 The NMR structure of a complex of the compound with H-Ras GTP(T35S), exclusively adopting the unique conformation, confirms its insertion into one of the surface pockets and provides a molecular basis for binding inhibition toward multiple Ras GTP-interacting molecules. Guanosine Triphosphate 244-247 HRas proto-oncogene, GTPase Homo sapiens 52-57 20858867-2 2010 Two overlapping regulatory networks control compartmentalized H-Ras activity: the guanosine diphosphate-guanosine triphosphate cycle and the acylation cycle, which constitutively traffics Ras isoforms that can be palmitoylated between intracellular membrane compartments. Guanosine Triphosphate 104-126 HRas proto-oncogene, GTPase Homo sapiens 62-67 20718707-1 2010 The small GTP-binding proteins HRAS, KRAS and NRAS belong to a family of oncoproteins associated with many types of human cancer. Guanosine Triphosphate 10-13 HRas proto-oncogene, GTPase Homo sapiens 31-35 22231449-5 2012 Furthermore, the binding is most efficient when H-Ras has a functional effector-binding loop, and is GTP-bound and ubiquitylated. Guanosine Triphosphate 101-104 HRas proto-oncogene, GTPase Homo sapiens 48-53 22845804-6 2012 The small molecules are therefore selecting biologically relevant conformations in the crystal that are sampled by the disordered switch II in the uncomplexed GTP-bound form of H-Ras. Guanosine Triphosphate 159-162 HRas proto-oncogene, GTPase Homo sapiens 177-182 21768877-1 2012 INTRODUCTION: The K-ras proto-oncogene encodes a protein (p21-ras) belonging to the family of GTP/GDP-binding proteins with GTPase activity. Guanosine Triphosphate 94-97 HRas proto-oncogene, GTPase Homo sapiens 58-65 21945529-3 2011 Here, we use a combination of multiple solvent crystal structures and computational solvent mapping (FTMap) to determine binding site hot spots in the "off" and "on" allosteric states of the GTP-bound form of H-Ras. Guanosine Triphosphate 191-194 HRas proto-oncogene, GTPase Homo sapiens 209-214 20018863-6 2010 On the other hand, the mant tag inhibits TSC2GAP-catalyzed GTP hydrolysis by Rheb but promotes p120 RasGAP-catalyzed GTP hydrolysis by H-Ras. Guanosine Triphosphate 117-120 HRas proto-oncogene, GTPase Homo sapiens 135-140 20700538-4 2010 In the current study we show that stabilizing the H-Ras-Gal-1 interaction, using bimolecular fluorescence complementation (BiFC), leads to prolonged immobilization of H-Ras.GTP in the plasma membrane which was measured by fluorescence recovery after photobleaching (FRAP), and increased signal out-put to the MAPK module. Guanosine Triphosphate 173-176 HRas proto-oncogene, GTPase Homo sapiens 167-172 20700538-5 2010 EM measurements of Raf recruitment to the H-Ras.GTP nanoclusters demonstrated that the enhanced signaling observed in the BiFC stabilized H-Ras.GTP nanocluster was attributed to increased H-Ras immobilization rather than to an increase in Raf recruitment. Guanosine Triphosphate 48-51 HRas proto-oncogene, GTPase Homo sapiens 42-47 20700538-5 2010 EM measurements of Raf recruitment to the H-Ras.GTP nanoclusters demonstrated that the enhanced signaling observed in the BiFC stabilized H-Ras.GTP nanocluster was attributed to increased H-Ras immobilization rather than to an increase in Raf recruitment. Guanosine Triphosphate 48-51 HRas proto-oncogene, GTPase Homo sapiens 138-143 20700538-5 2010 EM measurements of Raf recruitment to the H-Ras.GTP nanoclusters demonstrated that the enhanced signaling observed in the BiFC stabilized H-Ras.GTP nanocluster was attributed to increased H-Ras immobilization rather than to an increase in Raf recruitment. Guanosine Triphosphate 48-51 HRas proto-oncogene, GTPase Homo sapiens 138-143 20700538-5 2010 EM measurements of Raf recruitment to the H-Ras.GTP nanoclusters demonstrated that the enhanced signaling observed in the BiFC stabilized H-Ras.GTP nanocluster was attributed to increased H-Ras immobilization rather than to an increase in Raf recruitment. Guanosine Triphosphate 144-147 HRas proto-oncogene, GTPase Homo sapiens 42-47 20700538-5 2010 EM measurements of Raf recruitment to the H-Ras.GTP nanoclusters demonstrated that the enhanced signaling observed in the BiFC stabilized H-Ras.GTP nanocluster was attributed to increased H-Ras immobilization rather than to an increase in Raf recruitment. Guanosine Triphosphate 144-147 HRas proto-oncogene, GTPase Homo sapiens 138-143 20700538-5 2010 EM measurements of Raf recruitment to the H-Ras.GTP nanoclusters demonstrated that the enhanced signaling observed in the BiFC stabilized H-Ras.GTP nanocluster was attributed to increased H-Ras immobilization rather than to an increase in Raf recruitment. Guanosine Triphosphate 144-147 HRas proto-oncogene, GTPase Homo sapiens 138-143 20700538-3 2010 Upon activation, the GTP bound H-Ras binds to Galectin-1 (Gal-1) and becomes transiently immobilized in short-lived nanoclusters on the plasma membrane from which the signal is propagated to Raf. Guanosine Triphosphate 21-24 HRas proto-oncogene, GTPase Homo sapiens 31-36 20700538-4 2010 In the current study we show that stabilizing the H-Ras-Gal-1 interaction, using bimolecular fluorescence complementation (BiFC), leads to prolonged immobilization of H-Ras.GTP in the plasma membrane which was measured by fluorescence recovery after photobleaching (FRAP), and increased signal out-put to the MAPK module. Guanosine Triphosphate 173-176 HRas proto-oncogene, GTPase Homo sapiens 50-55 19995790-9 2010 Co-precipitation of GTP-bound HRAS(E37dup) by various effector proteins, however, was inefficient because of drastically diminished binding affinities. Guanosine Triphosphate 20-23 HRas proto-oncogene, GTPase Homo sapiens 30-34 19995790-10 2010 Thus, although HRAS(E37dup) is predominantly present in the active, GTP-bound state, it promotes only a weak hyperactivation of downstream signaling pathways. Guanosine Triphosphate 68-71 HRas proto-oncogene, GTPase Homo sapiens 15-19 18758236-7 2008 In the GTP-bound state, H-ras adopts an orientation that allows read out by Ras effectors and translation into corresponding MAPK signalling. Guanosine Triphosphate 7-10 HRas proto-oncogene, GTPase Homo sapiens 24-29 20080631-4 2010 These results rationalize the role of galectin-1 in generating active GTP-H-ras signaling nanoclusters. Guanosine Triphosphate 70-73 HRas proto-oncogene, GTPase Homo sapiens 74-79 18771285-4 2008 Here we present evidence that the conformational exchange process in human H-Ras complexed with GTP mimic GppNHp is global, encompassing most of the GTPase catalytic domain. Guanosine Triphosphate 96-99 HRas proto-oncogene, GTPase Homo sapiens 75-80 19995790-8 2010 Recombinant HRAS(E37dup) was characterized by slightly increased GTP/GDP dissociation, lower intrinsic GTPase activity and complete resistance to neurofibromin 1 GTPase-activating protein (GAP) stimulation due to dramatically reduced binding. Guanosine Triphosphate 65-68 HRas proto-oncogene, GTPase Homo sapiens 12-16 19035362-3 2009 HRAS is one of the three classical RAS proteins and cycles between an active, GTP- and an inactive, GDP-bound conformation. Guanosine Triphosphate 78-81 HRas proto-oncogene, GTPase Homo sapiens 0-4 19035362-5 2009 The GTP-bound form of HRAS was significantly enriched in CS compared with normal fibroblasts. Guanosine Triphosphate 4-7 HRas proto-oncogene, GTPase Homo sapiens 22-26 16980621-5 2006 Thus, clustering raft-associated HA proteins facilitated the early step whereby H-Ras is converted to an activated, GTP-loaded state but inhibited the ensuing step of downstream signaling via the Mek/Erk pathway. Guanosine Triphosphate 116-119 HRas proto-oncogene, GTPase Homo sapiens 80-85 18547521-4 2008 We demonstrate that GTP-bound and nucleotide-free G12V H-ras sample a wide region of conformational space, and show that the inactive-to-active transition is a multiphase process defined by the relative rearrangement of the two switches and the orientation of Tyr32. Guanosine Triphosphate 20-23 HRas proto-oncogene, GTPase Homo sapiens 55-60 18291096-1 2008 Previous (31)P NMR studies revealed that small GTPases H-Ras and K-Ras in complex with GTP assume two interconverting conformational states, state 1 and state 2. Guanosine Triphosphate 47-50 HRas proto-oncogene, GTPase Homo sapiens 55-60 17979197-2 2008 De novo heterozygous missense mutations in HRAS codon 12 and 13 disturbing the intrinsic GTP hydrolysis cause Costello syndrome. Guanosine Triphosphate 89-92 HRas proto-oncogene, GTPase Homo sapiens 43-47 17979197-4 2008 Recombinant HRAS p.Lys117Arg demonstrates normal intrinsic GTP hydrolysis and responsiveness to GTPase-activating proteins, but the nucleotide dissociation rate is increased 80-fold. Guanosine Triphosphate 59-62 HRas proto-oncogene, GTPase Homo sapiens 12-16 17497936-6 2007 Given that each of the nonhydrolyzable GTP analogues is able to promote the binding of RhoC to effector proteins, these results suggest that RhoC can undergo at least two conformational transitions during its conversion from a signaling-inactive to a signaling-active state, similar to what has recently been proposed for the H-Ras and M-Ras proteins. Guanosine Triphosphate 39-42 HRas proto-oncogene, GTPase Homo sapiens 326-331 18413234-8 2008 We further show that the N-terminal domain of Gal-3 interacts with and inhibits RasGRP4-mediated GTP loading on N-Ras and H-Ras proteins. Guanosine Triphosphate 97-100 HRas proto-oncogene, GTPase Homo sapiens 122-127 18344980-2 2008 HRas, NRas or KRas are mutated to remain in the active GTP-bound oncogenic state in many cancers. Guanosine Triphosphate 55-58 HRas proto-oncogene, GTPase Homo sapiens 0-4 16895916-1 2006 Phospholipase Cepsilon (PLCepsilon) is a newly described effector of the small GTP-binding protein H-Ras. Guanosine Triphosphate 79-82 HRas proto-oncogene, GTPase Homo sapiens 99-104 16481401-10 2006 GRFdeltaC binds H-Ras.GTP in both pulldown assays from bacterial lysates and by coimmunoprecipitation from HEK293 cells. Guanosine Triphosphate 22-25 HRas proto-oncogene, GTPase Homo sapiens 16-21 16569214-8 2006 Assays for GTP loading and H-Ras interactions with the Ras-binding domain on Raf-1 demonstrated a decrease in H-Ras activity in the presence of NO*. Guanosine Triphosphate 11-14 HRas proto-oncogene, GTPase Homo sapiens 110-115 15789417-1 2005 Controlling the hydrolysis rate of GTP bound to the p21ras protein is crucial for the delicate timing of many biological processes. Guanosine Triphosphate 35-38 HRas proto-oncogene, GTPase Homo sapiens 52-58 16488996-6 2006 Epidermal growth factor stimulation rapidly increases active H-Ras-GTP and phosphorylated extracellular signal-regulated kinase (ERK) on rasosomes. Guanosine Triphosphate 67-70 HRas proto-oncogene, GTPase Homo sapiens 61-66 16024806-4 2005 However, once at the plasma membrane, monopalmitoylation of Cys184 supports correct GTP-regulated lateral segregation of H-ras between cholesterol-dependent and cholesterol-independent microdomains. Guanosine Triphosphate 84-87 HRas proto-oncogene, GTPase Homo sapiens 121-126 16024806-5 2005 In contrast, monopalmitoylation of Cys181 dramatically reverses H-ras lateral segregation, driving GTP-loaded H-ras into cholesterol-dependent microdomains. Guanosine Triphosphate 99-102 HRas proto-oncogene, GTPase Homo sapiens 64-69 16024806-5 2005 In contrast, monopalmitoylation of Cys181 dramatically reverses H-ras lateral segregation, driving GTP-loaded H-ras into cholesterol-dependent microdomains. Guanosine Triphosphate 99-102 HRas proto-oncogene, GTPase Homo sapiens 110-115 16024806-6 2005 Intriguingly, the Cys181 monopalmitoylated H-ras anchor emulates the GTP-regulated microdomain interactions of N-ras. Guanosine Triphosphate 69-72 HRas proto-oncogene, GTPase Homo sapiens 43-48 15789417-3 2005 To gain more insight into the individual elementary events of GTP hydrolysis, we carried out molecular dynamic analysis of wild-type p21ras and some of its mutants. Guanosine Triphosphate 62-65 HRas proto-oncogene, GTPase Homo sapiens 133-139 15355981-5 2004 Furthermore analysis of the signals obtained suggested activation of p21Ras by lipopolysaccharide, and this was confirmed by direct measurement of p21Ras GTP levels in lipopolysaccharide-stimulated human peripheral blood mononuclear cells, which represents the first direct demonstration of p21Ras activation by stimulation of a Toll receptor family member. Guanosine Triphosphate 154-157 HRas proto-oncogene, GTPase Homo sapiens 69-75 15812354-2 2005 METHODS: p21Ras functional activity was analyzed by direct measurement of GTP/GDP ratio in anti-p21Ras immunoprecipitates of K562 cells previously incubated with H3(32)PO4. Guanosine Triphosphate 74-77 HRas proto-oncogene, GTPase Homo sapiens 9-15 15812354-2 2005 METHODS: p21Ras functional activity was analyzed by direct measurement of GTP/GDP ratio in anti-p21Ras immunoprecipitates of K562 cells previously incubated with H3(32)PO4. Guanosine Triphosphate 74-77 HRas proto-oncogene, GTPase Homo sapiens 96-102 15860728-1 2005 Recent studies show that the partitioning of the small GTPase H-Ras in different types of membrane microdomains is dependent on guanosine 5"-triphosphate (GTP)-loading of H-Ras. Guanosine Triphosphate 128-153 HRas proto-oncogene, GTPase Homo sapiens 62-67 15860728-1 2005 Recent studies show that the partitioning of the small GTPase H-Ras in different types of membrane microdomains is dependent on guanosine 5"-triphosphate (GTP)-loading of H-Ras. Guanosine Triphosphate 128-153 HRas proto-oncogene, GTPase Homo sapiens 171-176 15860728-1 2005 Recent studies show that the partitioning of the small GTPase H-Ras in different types of membrane microdomains is dependent on guanosine 5"-triphosphate (GTP)-loading of H-Ras. Guanosine Triphosphate 55-58 HRas proto-oncogene, GTPase Homo sapiens 62-67 15860728-1 2005 Recent studies show that the partitioning of the small GTPase H-Ras in different types of membrane microdomains is dependent on guanosine 5"-triphosphate (GTP)-loading of H-Ras. Guanosine Triphosphate 55-58 HRas proto-oncogene, GTPase Homo sapiens 171-176 15355981-5 2004 Furthermore analysis of the signals obtained suggested activation of p21Ras by lipopolysaccharide, and this was confirmed by direct measurement of p21Ras GTP levels in lipopolysaccharide-stimulated human peripheral blood mononuclear cells, which represents the first direct demonstration of p21Ras activation by stimulation of a Toll receptor family member. Guanosine Triphosphate 154-157 HRas proto-oncogene, GTPase Homo sapiens 147-153 15355981-5 2004 Furthermore analysis of the signals obtained suggested activation of p21Ras by lipopolysaccharide, and this was confirmed by direct measurement of p21Ras GTP levels in lipopolysaccharide-stimulated human peripheral blood mononuclear cells, which represents the first direct demonstration of p21Ras activation by stimulation of a Toll receptor family member. Guanosine Triphosphate 154-157 HRas proto-oncogene, GTPase Homo sapiens 147-153 15254246-0 2004 Three separable domains regulate GTP-dependent association of H-ras with the plasma membrane. Guanosine Triphosphate 33-36 HRas proto-oncogene, GTPase Homo sapiens 62-67 15287738-1 2004 p21Ras (Ras) proteins cycle between active GTP-bound and inactive GDP-bound states to mediate signal transduction pathways that promote cell growth, differentiation, and apoptosis. Guanosine Triphosphate 43-46 HRas proto-oncogene, GTPase Homo sapiens 0-6 15254246-6 2004 Operating against the attractive interaction of the lipid anchor for lipid rafts is a repulsive force generated by the N-terminal catalytic domain that increases when H-ras is GTP loaded. Guanosine Triphosphate 176-179 HRas proto-oncogene, GTPase Homo sapiens 167-172 15254246-7 2004 These observations lead directly to a novel mechanism that explains how H-ras lateral segregation is regulated by activation state: GTP loading decreases H-ras affinity for lipid rafts and allows the hypervariable linker domain to target to nonraft microdomains, the primary site of H-ras signaling. Guanosine Triphosphate 132-135 HRas proto-oncogene, GTPase Homo sapiens 72-77 15254246-7 2004 These observations lead directly to a novel mechanism that explains how H-ras lateral segregation is regulated by activation state: GTP loading decreases H-ras affinity for lipid rafts and allows the hypervariable linker domain to target to nonraft microdomains, the primary site of H-ras signaling. Guanosine Triphosphate 132-135 HRas proto-oncogene, GTPase Homo sapiens 154-159 15254246-7 2004 These observations lead directly to a novel mechanism that explains how H-ras lateral segregation is regulated by activation state: GTP loading decreases H-ras affinity for lipid rafts and allows the hypervariable linker domain to target to nonraft microdomains, the primary site of H-ras signaling. Guanosine Triphosphate 132-135 HRas proto-oncogene, GTPase Homo sapiens 154-159 14978301-2 2004 We investigated the 3D context of these regions observed in 28 protein structures containing a GTP-binding domain assumed to be homologous to the transforming factor p21-RAS. Guanosine Triphosphate 95-98 HRas proto-oncogene, GTPase Homo sapiens 166-173 12569357-5 2003 This mutant, H-Ras (K117E), was found to be constitutively activated in terms of GTP binding. Guanosine Triphosphate 81-84 HRas proto-oncogene, GTPase Homo sapiens 13-18 11906819-10 2002 Finally, the levels of three small guanosine-5"-triphosphate (GTP) binding proteins were screened upon differentiation showing rab3A to be increased while rhoA and H-ras were decreased. Guanosine Triphosphate 62-65 HRas proto-oncogene, GTPase Homo sapiens 164-169 12149263-6 2002 Here we show that in comparison with Ras transfectants, H-Ras/galectin-1 or K-Ras4B/galectin-1 co-transfectants exhibit enhanced and prolonged epidermal growth factor (EGF)-stimulated increases in Ras-GTP, Raf-1 activity, and active extracellular signal-regulated kinase. Guanosine Triphosphate 201-204 HRas proto-oncogene, GTPase Homo sapiens 56-61 12359913-4 2002 Using a novel fluorescent probe monitoring GTP-bound Ras in live cells (GFP-Raf-1-RBS), Golgi-associated H-Ras was shown to be activated in situ after growth factor stimulation, with kinetics distinct from that of H-Ras activation at the plasma membrane. Guanosine Triphosphate 43-46 HRas proto-oncogene, GTPase Homo sapiens 105-110 12006650-4 2002 H-Ras and K-Ras fusion proteins were found at the plasma membrane, particularly in ruffles and lamellipodia, and also in endosomes independently of GTP/GDP loading and EGF stimulation. Guanosine Triphosphate 148-151 HRas proto-oncogene, GTPase Homo sapiens 0-5 11676197-6 2001 Coordinately, the ratio of p21ras-binding GTP/GDP was increased by PLM. Guanosine Triphosphate 42-45 HRas proto-oncogene, GTPase Homo sapiens 27-33 11593050-4 2001 This screen is based on the observation that the activation of the small guanosine triphosphate (GTP)-binding protein H-Ras initiates a mitogen-activated protein kinase (MAPK)-dependent signaling pathway that inactivates integrin ligand binding. Guanosine Triphosphate 73-95 HRas proto-oncogene, GTPase Homo sapiens 118-123 11593050-4 2001 This screen is based on the observation that the activation of the small guanosine triphosphate (GTP)-binding protein H-Ras initiates a mitogen-activated protein kinase (MAPK)-dependent signaling pathway that inactivates integrin ligand binding. Guanosine Triphosphate 97-100 HRas proto-oncogene, GTPase Homo sapiens 118-123 12032842-1 2002 v-H-ras transformed C2C12 (C2Ras) myoblasts, overexpressing p21-Ras protein in the Ras-GTP active form, showed a differentiation-defective phenotype when cultured in low serum as compared with C2C12 myoblasts. Guanosine Triphosphate 87-90 HRas proto-oncogene, GTPase Homo sapiens 60-67 11283610-0 2001 GTP-dependent segregation of H-ras from lipid rafts is required for biological activity. Guanosine Triphosphate 0-3 HRas proto-oncogene, GTPase Homo sapiens 29-34 11309191-6 2001 K-Ras is localized predominantly to the disordered plasma membrane, whereas H-Ras exists in a GTP-regulated equilibrium between disordered plasma membrane and cholesterol-rich lipid rafts. Guanosine Triphosphate 94-97 HRas proto-oncogene, GTPase Homo sapiens 76-81 11283610-3 2001 GTP-loading redistributes H-ras from rafts into bulk plasma membrane by a mechanism that requires the adjacent hypervariable region of H-ras. Guanosine Triphosphate 0-3 HRas proto-oncogene, GTPase Homo sapiens 26-31 11283610-3 2001 GTP-loading redistributes H-ras from rafts into bulk plasma membrane by a mechanism that requires the adjacent hypervariable region of H-ras. Guanosine Triphosphate 0-3 HRas proto-oncogene, GTPase Homo sapiens 135-140 11179219-3 2001 The RA2 domain binds H-Ras in a GTP-dependent manner, comparable with the Ras-binding domain of Raf-1; however, the RA1 domain binds H-Ras with a low affinity in a GTP-independent manner. Guanosine Triphosphate 164-167 HRas proto-oncogene, GTPase Homo sapiens 133-138 11313946-1 2001 Here, we report the identification and characterization of a new member of the RalGDS-family, which is widely expressed and interacts strongly and selectively with the GTP-bound forms of M-Ras and p21 Ras. Guanosine Triphosphate 168-171 HRas proto-oncogene, GTPase Homo sapiens 197-204 11283610-6 2001 Our studies identify a novel protein determinant that is required for H-ras function, and show that the GTP/GDP state of H-ras determines its lateral segregation on the plasma membrane. Guanosine Triphosphate 104-107 HRas proto-oncogene, GTPase Homo sapiens 121-126 9780005-8 1998 Injection of antibodies to p21ras itself, or a recombinant Raf-1 protein domain which binds to the effector region of ras in a GTP-dependent manner, results in the inhibition of cell cycle progression throughout G1 phase. Guanosine Triphosphate 127-130 HRas proto-oncogene, GTPase Homo sapiens 27-33 11188692-1 2000 BACKGROUND: The means by which the protein GAP accelerates GTP hydrolysis, and thereby downregulates growth signaling by p21Ras, is of considerable interest, particularly inasmuch as p21 mutants are implicated in a number of human cancers. Guanosine Triphosphate 59-62 HRas proto-oncogene, GTPase Homo sapiens 121-127 10595559-6 1999 For 2"-halogenated GTP analogues, the kinetics of interaction were determined for the small GTPases p21ras(Y32W) (fluorescent mutant) and RabS. Guanosine Triphosphate 19-22 HRas proto-oncogene, GTPase Homo sapiens 100-106 10453987-6 1999 We also showed an increased level of GTP in p21Ras immunoprecipitates from IGF-I treated cells. Guanosine Triphosphate 37-40 HRas proto-oncogene, GTPase Homo sapiens 44-50 11179219-3 2001 The RA2 domain binds H-Ras in a GTP-dependent manner, comparable with the Ras-binding domain of Raf-1; however, the RA1 domain binds H-Ras with a low affinity in a GTP-independent manner. Guanosine Triphosphate 32-35 HRas proto-oncogene, GTPase Homo sapiens 21-26 10607402-7 1999 Furthermore, display of cysteine-free Ras is demonstrated by GTP-analogue dependent binding to the Ras-binding domain of the Ras-effector Raf1. Guanosine Triphosphate 61-64 HRas proto-oncogene, GTPase Homo sapiens 38-41 10607402-7 1999 Furthermore, display of cysteine-free Ras is demonstrated by GTP-analogue dependent binding to the Ras-binding domain of the Ras-effector Raf1. Guanosine Triphosphate 61-64 HRas proto-oncogene, GTPase Homo sapiens 99-102 10607402-7 1999 Furthermore, display of cysteine-free Ras is demonstrated by GTP-analogue dependent binding to the Ras-binding domain of the Ras-effector Raf1. Guanosine Triphosphate 61-64 HRas proto-oncogene, GTPase Homo sapiens 99-102 10208427-4 1999 Furthermore, the ratio of GTP/GDP bound to cellular p21ras was consistently higher in the hSos1-Isf II-transfected clones, both under basal and stimulated conditions. Guanosine Triphosphate 26-29 HRas proto-oncogene, GTPase Homo sapiens 52-58 9778365-1 1998 p21(H-ras) plays a critical role in signal transduction pathways by cycling between an active, GTP/Mg2+ ternary complex and an inactive, GDP/Mg2+ complex. Guanosine Triphosphate 95-98 HRas proto-oncogene, GTPase Homo sapiens 4-9 9760267-1 1998 Transient kinetic methods have been used to analyze the interaction between the Ras-binding domain (RBD) of c-Raf-1 and a complex of H-Ras and a GTP analogue. Guanosine Triphosphate 145-148 HRas proto-oncogene, GTPase Homo sapiens 133-138 9760267-4 1998 The lifetime of the complex is therefore on the order of 50-100 ms, which is much shorter than the lifetime of GTP at the active site of H-Ras as determined by the intrinsic GTPase reaction. Guanosine Triphosphate 111-114 HRas proto-oncogene, GTPase Homo sapiens 137-142 9760267-6 1998 The GDP complex of H-Ras binds more than 2 orders of magnitude more weakly than the GTP-analogue complex, mainly due to a significant weakening of the initial binding equilibrium reaction in the GDP state, thereby avoiding even short-lived recruitment of Raf to the plasma membrane by the inactive Ras form. Guanosine Triphosphate 84-87 HRas proto-oncogene, GTPase Homo sapiens 19-24 9405284-4 1998 The activation of extracellular signal-related protein kinases (ERKs) is correlated with the activation of p21ras by both tyrosine kinase and G-protein-coupled receptors as measured by a novel assay for GTP loading. Guanosine Triphosphate 203-206 HRas proto-oncogene, GTPase Homo sapiens 107-113 9619634-8 1998 Retinoic acid (RA)-induced differentiation and growth inhibition of neuroblastoma cells was associated with an increase in type 1 GAP120 and neurofibromin mRNA, and a decrease in p21ras-GTP. Guanosine Triphosphate 186-189 HRas proto-oncogene, GTPase Homo sapiens 179-185 9620547-3 1998 We found that binding of PtdIns4,5P2 to 6-his-tagged recombinant mSOS in vitro inhibits the ability of SOS to catalyze the association of GTP on p21RAS. Guanosine Triphosphate 138-141 HRas proto-oncogene, GTPase Homo sapiens 145-151 9545299-6 1998 Compared with H-Ras and other GTPases bound to GTP or GTP analogues, the significant conformational differences are located in regions involving switches I and II and part of the antiparallel beta-sheet between switches I and II. Guanosine Triphosphate 47-50 HRas proto-oncogene, GTPase Homo sapiens 14-19 9516156-9 1998 Activation kinetics correlated with activation of p21ras by both cytokines and chemoattractants as measured by a novel assay for guanosine triphosphate (GTP)-loading. Guanosine Triphosphate 129-151 HRas proto-oncogene, GTPase Homo sapiens 50-56 9516156-9 1998 Activation kinetics correlated with activation of p21ras by both cytokines and chemoattractants as measured by a novel assay for guanosine triphosphate (GTP)-loading. Guanosine Triphosphate 153-156 HRas proto-oncogene, GTPase Homo sapiens 50-56 9619634-3 1998 Increased levels of p21ras-GTP (active) have been associated with increased cell growth and malignant transformation. Guanosine Triphosphate 27-30 HRas proto-oncogene, GTPase Homo sapiens 20-26 9619634-6 1998 However, the amount of p21ras-GTP bound was higher in pPNET than in neuroblastoma cells. Guanosine Triphosphate 30-33 HRas proto-oncogene, GTPase Homo sapiens 23-29 9404480-3 1997 These changes alter the conformation of the protein resulting in insensitivity of the protein to the GTPase activating protein which normally hydrolyses the active p21RAS GTP-bound form to the inactive GDP-bound form. Guanosine Triphosphate 101-104 HRas proto-oncogene, GTPase Homo sapiens 164-170 9437002-4 1998 In p21 Ras, the alpha2 helix of the Switch 2 domain undergoes a major conformational change upon GTP hydrolysis. Guanosine Triphosphate 97-100 HRas proto-oncogene, GTPase Homo sapiens 3-10 9345266-0 1997 GTP loading of farnesylated p21Ras by insulin at the plasma membrane. Guanosine Triphosphate 0-3 HRas proto-oncogene, GTPase Homo sapiens 28-34 9345266-6 1997 We have also observed a direct correlation between the amounts of farnesylated p21Ras at the plasma membrane and the magnitude of insulin-induced GTP loading of p21Ras. Guanosine Triphosphate 146-149 HRas proto-oncogene, GTPase Homo sapiens 79-85 9345266-6 1997 We have also observed a direct correlation between the amounts of farnesylated p21Ras at the plasma membrane and the magnitude of insulin-induced GTP loading of p21Ras. Guanosine Triphosphate 146-149 HRas proto-oncogene, GTPase Homo sapiens 161-167 9312017-8 1997 The conformational changes between the GDP and GTP complexes are located essentially in the switch I and II regions as described for the related oncoprotein H-Ras. Guanosine Triphosphate 47-50 HRas proto-oncogene, GTPase Homo sapiens 157-162 9112423-2 1997 Cells preincubated with 100 nM insulin for 24 or 48 hours exhibited further 5-8 fold increases in p21Ras.GTP loading in response to an acute (10 minute) challenge with either insulin, EGF, or IGF-1. Guanosine Triphosphate 105-108 HRas proto-oncogene, GTPase Homo sapiens 98-104 8916907-0 1996 Linear free energy relationships in the intrinsic and GTPase activating protein-stimulated guanosine 5"-triphosphate hydrolysis of p21ras. Guanosine Triphosphate 91-116 HRas proto-oncogene, GTPase Homo sapiens 131-137 9102473-0 1997 The role of the metal ion in the p21ras catalysed GTP-hydrolysis: Mn2+ versus Mg2+. Guanosine Triphosphate 50-53 HRas proto-oncogene, GTPase Homo sapiens 33-39 9102473-3 1997 It is shown here for p21ras, a well studied example of GTP hydrolysing proteins, that the GTP-hydrolysis rate is significantly faster if Mg2+ is replaced by Mn2+, both in the presence or absence of its GTPase-activating protein Ras-GAP. Guanosine Triphosphate 55-58 HRas proto-oncogene, GTPase Homo sapiens 21-27 9102473-3 1997 It is shown here for p21ras, a well studied example of GTP hydrolysing proteins, that the GTP-hydrolysis rate is significantly faster if Mg2+ is replaced by Mn2+, both in the presence or absence of its GTPase-activating protein Ras-GAP. Guanosine Triphosphate 90-93 HRas proto-oncogene, GTPase Homo sapiens 21-27 8916907-2 1996 Theoretical, structural, and functional studies have demonstrated that in p21ras the substrate of the reaction, GTP itself, plays a central role by acting as the base catalyst. Guanosine Triphosphate 112-115 HRas proto-oncogene, GTPase Homo sapiens 74-80 8916907-12 1996 We also analyzed the stimulated GTPase reaction of p21ras by the GTPase activating protein (GAP) and the GTPase reaction of Rap1A, a Ras-related GTP binding protein, with similar approaches. Guanosine Triphosphate 32-35 HRas proto-oncogene, GTPase Homo sapiens 51-57 8916908-1 1996 Previous studies of the GTPase reaction catalyzed by p21ras have indicated that the logarithm of the observed reaction rate and the pKa of the bound GTP are correlated by the Bronsted relationship log(kcat) = beta pKa + A. Guanosine Triphosphate 24-27 HRas proto-oncogene, GTPase Homo sapiens 53-59 7559502-5 1995 Nonetheless, the desensitization of p21ras in response to these stimuli was homologous, in that each peptide could reactivate [32P]GTP loading of p21ras after desensitization by any of the others. Guanosine Triphosphate 131-134 HRas proto-oncogene, GTPase Homo sapiens 36-42 8798525-1 1996 Mammalian H-Ras and N-Ras are GTP-binding proteins that must be post-translationally lipidated to function as molecular switches in signal transduction cascades controlling cell growth and differentiation. Guanosine Triphosphate 30-33 HRas proto-oncogene, GTPase Homo sapiens 10-15 8974153-5 1996 p21ras functions as a molecular switch active when GTP is bound to it and inactive in the GDP-bound form. Guanosine Triphosphate 51-54 HRas proto-oncogene, GTPase Homo sapiens 0-6 8756686-1 1996 31P NMR revealed that the complex of p21ras with the GTP analog GppNHp.Mg2+ exists in two conformational states, states 1 and 2. Guanosine Triphosphate 53-56 HRas proto-oncogene, GTPase Homo sapiens 37-43 8710888-2 1996 In the present study, we plated human neutrophils on surface-bound anti-beta 2 (CD18) antibodies and found that the small GTP-binding protein p21ras is activated by beta 2 integrins. Guanosine Triphosphate 122-125 HRas proto-oncogene, GTPase Homo sapiens 142-148 8765045-1 1996 Ligation of the B cell antigen receptor (BCR) complex initiates tyrosine phosphorylation of the receptor"s transducer components, Ig-alpha and Ig-beta and tyrosine kinase-dependent accumulation of GTP-bound, activated p21ras. Guanosine Triphosphate 197-200 HRas proto-oncogene, GTPase Homo sapiens 218-224 8740369-0 1996 Electrostatic control of GTP and GDP binding in the oncoprotein p21ras. Guanosine Triphosphate 25-28 HRas proto-oncogene, GTPase Homo sapiens 64-70 8740369-2 1996 The GTP-bound form of p21ras sends a growth-promoting signal that is terminated once the protein is cycled back into its GDP-bound form. Guanosine Triphosphate 4-7 HRas proto-oncogene, GTPase Homo sapiens 22-28 8740369-3 1996 The interaction of guanine-nucleotide-exchange factors (GEFs) with p21ras leads to activation of the protein by promoting GDP --> GTP exchange. Guanosine Triphosphate 133-136 HRas proto-oncogene, GTPase Homo sapiens 67-73 8740369-4 1996 Oncogenic mutations of p21ras trap the protein in its biological active GTP-bound form. Guanosine Triphosphate 72-75 HRas proto-oncogene, GTPase Homo sapiens 23-29 8740369-7 1996 RESULTS: The crystal structures of p21ras are correlated with the binding affinities of GTP and GDP by calculating the relevant electrostatic energies. Guanosine Triphosphate 88-91 HRas proto-oncogene, GTPase Homo sapiens 35-41 8626511-1 1996 We examined the effects of the Gly-60 to Ala mutation on the interaction of H-Ras with Ras GTPase activating protein (GAP), neurofibromin 1 (NF1), Raf-1, and ral guanine nucleotide dissociation stimulator (ralGDS), factors that interact with GTP-bound form of H-Ras. Guanosine Triphosphate 91-94 HRas proto-oncogene, GTPase Homo sapiens 76-81 8626511-3 1996 We found that the G60A mutation decreases GTPase activity of H-Ras without significantly affecting GTP/GDP binding. Guanosine Triphosphate 42-45 HRas proto-oncogene, GTPase Homo sapiens 61-66 8626511-7 1996 These results indicate that although GAP, NF1, Raf-1, and ralGDS all interact with H-Ras in a GTP-dependent manner and they are able to compete against each other for binding to H-Ras, these factors share overlapping but not identical binding domains on H-Ras. Guanosine Triphosphate 94-97 HRas proto-oncogene, GTPase Homo sapiens 83-88 8626511-7 1996 These results indicate that although GAP, NF1, Raf-1, and ralGDS all interact with H-Ras in a GTP-dependent manner and they are able to compete against each other for binding to H-Ras, these factors share overlapping but not identical binding domains on H-Ras. Guanosine Triphosphate 94-97 HRas proto-oncogene, GTPase Homo sapiens 178-183 8626511-7 1996 These results indicate that although GAP, NF1, Raf-1, and ralGDS all interact with H-Ras in a GTP-dependent manner and they are able to compete against each other for binding to H-Ras, these factors share overlapping but not identical binding domains on H-Ras. Guanosine Triphosphate 94-97 HRas proto-oncogene, GTPase Homo sapiens 178-183 8636102-0 1996 Differential interaction of the ras family GTP-binding proteins H-Ras, Rap1A, and R-Ras with the putative effector molecules Raf kinase and Ral-guanine nucleotide exchange factor. Guanosine Triphosphate 43-46 HRas proto-oncogene, GTPase Homo sapiens 64-69 7492562-1 1995 The rate of GTP hydrolysis on p21ras is accelerated by approximately 10(5) times by the catalytic domains of GTPase-activating proteins (GAPs), p120-GAP (GAP-344) or neurofibromin (NF1-334). Guanosine Triphosphate 12-15 HRas proto-oncogene, GTPase Homo sapiens 30-36 7492562-3 1995 Measurements were made in real time with a stopped-flow apparatus, in which the p21ras complex with the 2",3"-methanthraniloyl analogue of GTP (mantGTP) was mixed with the GAP in the presence of this Pi probe. Guanosine Triphosphate 139-142 HRas proto-oncogene, GTPase Homo sapiens 80-86 7592690-1 1995 Insulin and epidermal growth factor receptors transmit signals for cell proliferation and gene regulation through formation of active GTP-bound p21ras mediated by the guanine nucleotide exchange factor Sos. Guanosine Triphosphate 134-137 HRas proto-oncogene, GTPase Homo sapiens 144-150 7559502-5 1995 Nonetheless, the desensitization of p21ras in response to these stimuli was homologous, in that each peptide could reactivate [32P]GTP loading of p21ras after desensitization by any of the others. Guanosine Triphosphate 131-134 HRas proto-oncogene, GTPase Homo sapiens 146-152 21153201-1 1995 Insulin increases activity of the guanine nucleotide exchange factor (GEF) in Rat-1 fibroblasts transfected with human insulin receptors (HIRc cells), thereby promoting formation of the active form of p21Ras (p21Ras GTP). Guanosine Triphosphate 216-219 HRas proto-oncogene, GTPase Homo sapiens 201-207 7542586-3 1995 We show that in mammalian cells activation of p74Raf-1 by oncogenic Src requires pp60Src to be myristoylated and the ability of p74Raf-1 to interact with p21Ras-GTP. Guanosine Triphosphate 161-164 HRas proto-oncogene, GTPase Homo sapiens 154-160 7542586-4 1995 The Ras/Raf interaction is required for p21Ras-GTP to bring p74Raf-1 to the plasma membrane for phosphorylation at tyrosine 340 or 341, probably by membrane-bound pp60Src. Guanosine Triphosphate 47-50 HRas proto-oncogene, GTPase Homo sapiens 40-46 7542586-6 1995 Thus, p21Ras-GTP is the limiting component in bringing p74Raf-1 to the plasma membrane for tyrosine phosphorylation. Guanosine Triphosphate 13-16 HRas proto-oncogene, GTPase Homo sapiens 6-12 7542586-7 1995 Using mutants of Raf-1 at Tyr340/341, we show that in addition to tyrosine phosphorylation at these sites, there is an additional activation step resulting from p21Ras-GTP recruiting p74Raf-1 to the plasma membrane. Guanosine Triphosphate 168-171 HRas proto-oncogene, GTPase Homo sapiens 161-167 7608150-2 1995 This hypothesis was tested in the present studies by evaluating the ability of truncation and deletion mutants of Drosophila (d)Sos to enhance [32P]GTP loading of p21ras when expressed in 32P-labeled COS or 293 cells. Guanosine Triphosphate 148-151 HRas proto-oncogene, GTPase Homo sapiens 163-169 7576990-4 1995 After a ligand binds to growth factor receptors, in particular receptor tyrosine kinases, a guanine nucleotide exchange factor is activated, which results in p21ras in the GTP-bound form. Guanosine Triphosphate 172-175 HRas proto-oncogene, GTPase Homo sapiens 158-164 7576990-5 1995 This GTP-bound form of p21ras interacts with the protein kinase raf1 and induces the activation of a kinase cascade, resulting in various cellular responses. Guanosine Triphosphate 5-8 HRas proto-oncogene, GTPase Homo sapiens 23-29 21153201-1 1995 Insulin increases activity of the guanine nucleotide exchange factor (GEF) in Rat-1 fibroblasts transfected with human insulin receptors (HIRc cells), thereby promoting formation of the active form of p21Ras (p21Ras GTP). Guanosine Triphosphate 216-219 HRas proto-oncogene, GTPase Homo sapiens 209-215 7706235-2 1995 Here, we report that nitric oxide (NO) activates p21ras in human T cells as evidenced by an increase in GTP-bound p21ras. Guanosine Triphosphate 104-107 HRas proto-oncogene, GTPase Homo sapiens 49-55 7613138-2 1995 IL-5 also stimulates GTP binding to p21ras. Guanosine Triphosphate 21-24 HRas proto-oncogene, GTPase Homo sapiens 36-42 7737275-10 1995 Finally, immunoblotting shows that CD28 also associates with the gene product of the human homolog of the Drosophila Son of sevenless gene (SOS), a GRB-2-complexed guanine nucleotide exchange factor responsible for converting p21ras to a GTP-bound active state. Guanosine Triphosphate 238-241 HRas proto-oncogene, GTPase Homo sapiens 226-232 7706235-4 1995 Circular dichroism analysis reveals that NO induces a profound conformational change in p21ras in association with GDP/GTP exchange. Guanosine Triphosphate 119-122 HRas proto-oncogene, GTPase Homo sapiens 88-94 7819254-1 1995 The interaction of the protein product of the H-ras oncogene with a series of nucleoside di- and triphosphates has been examined to investigate the tolerance of the active site to departures from the GTP or GDP structures. Guanosine Triphosphate 200-203 HRas proto-oncogene, GTPase Homo sapiens 46-51 7880841-0 1995 Mutagenesis of the H-ras p21 at glycine-60 residue disrupts GTP-induced conformational change. Guanosine Triphosphate 60-63 HRas proto-oncogene, GTPase Homo sapiens 19-24 7880841-5 1995 GTP induces an enhancement of fluorescence emission in complexes consisting of H-ras and the fluorescent dye 8-anilino-1-naphthalenesulfonic acid. Guanosine Triphosphate 0-3 HRas proto-oncogene, GTPase Homo sapiens 79-84 7880841-7 1995 On the basis of these observations, we propose that the GTP-induced conformational change of H-ras, a process required for H-ras activities, is impaired by the G60A mutation. Guanosine Triphosphate 56-59 HRas proto-oncogene, GTPase Homo sapiens 93-98 7880841-7 1995 On the basis of these observations, we propose that the GTP-induced conformational change of H-ras, a process required for H-ras activities, is impaired by the G60A mutation. Guanosine Triphosphate 56-59 HRas proto-oncogene, GTPase Homo sapiens 123-128 7806540-7 1994 Cell lines expressing mutant Y1158,Y1162F,Y1163F (YFF) receptors showed insulin-induced tyrosine phosphorylation of Shc, Shc.Grb2 complex formation, and p21ras-GTP formation, whereas tyrosine phosphorylation of IRS1 was strongly decreased and formation of IRS1.Grb2 complexes was undetectable. Guanosine Triphosphate 160-163 HRas proto-oncogene, GTPase Homo sapiens 153-159 7719852-0 1995 Substrate-assisted catalysis as a mechanism for GTP hydrolysis of p21ras and other GTP-binding proteins. Guanosine Triphosphate 48-51 HRas proto-oncogene, GTPase Homo sapiens 66-72 7719852-0 1995 Substrate-assisted catalysis as a mechanism for GTP hydrolysis of p21ras and other GTP-binding proteins. Guanosine Triphosphate 83-86 HRas proto-oncogene, GTPase Homo sapiens 66-72 7719852-4 1995 Here we present a unique type of linear free energy relationships that not only supports a mechanism for p21ras in which the substrate GTP itself acts as the catalytic base driving the GTPase reaction but can also help to explain why certain mutants of p21ras are oncogenic and others are not. Guanosine Triphosphate 135-138 HRas proto-oncogene, GTPase Homo sapiens 105-111 7719852-4 1995 Here we present a unique type of linear free energy relationships that not only supports a mechanism for p21ras in which the substrate GTP itself acts as the catalytic base driving the GTPase reaction but can also help to explain why certain mutants of p21ras are oncogenic and others are not. Guanosine Triphosphate 135-138 HRas proto-oncogene, GTPase Homo sapiens 253-259 7806540-0 1994 A mutant insulin receptor induces formation of a Shc-growth factor receptor bound protein 2 (Grb2) complex and p21ras-GTP without detectable interaction of insulin receptor substrate 1 (IRS1) with Grb2. Guanosine Triphosphate 118-121 HRas proto-oncogene, GTPase Homo sapiens 111-117 7806540-1 1994 Evidence for IRS1-independent p21ras-GTP formation. Guanosine Triphosphate 37-40 HRas proto-oncogene, GTPase Homo sapiens 30-36 7806540-3 1994 Insulin receptors induce p21ras-GTP formation by two possible mechanisms: tyrosine phosphorylation of insulin receptor substrate 1 (IRS1) and its subsequent association with Grb2, or Shc phosphorylation and its subsequent association with Grb2. Guanosine Triphosphate 32-35 HRas proto-oncogene, GTPase Homo sapiens 25-31 7806540-8 1994 The activity of FYY and YFF receptors to mediate p21ras-GTP formation correlated with their activity to induce Shc phosphorylation and Shc.Grb2 association. Guanosine Triphosphate 56-59 HRas proto-oncogene, GTPase Homo sapiens 49-55 7806540-10 1994 We conclude that phosphorylation of Tyr1158 and Tyr1162 of the insulin receptor is linked to distinct post-receptor processes and that YFF receptors generate p21ras-GTP via the Shc.Grb2 pathway rather than one involving IRS1.Grb2 interaction. Guanosine Triphosphate 165-168 HRas proto-oncogene, GTPase Homo sapiens 158-164 7949098-2 1994 NF1 encodes a protein called neurofibromin, which accelerates guanosine triphosphate (GTP) hydrolysis on the p21ras (Ras) family of signaling proteins. Guanosine Triphosphate 62-84 HRas proto-oncogene, GTPase Homo sapiens 109-115 7949098-2 1994 NF1 encodes a protein called neurofibromin, which accelerates guanosine triphosphate (GTP) hydrolysis on the p21ras (Ras) family of signaling proteins. Guanosine Triphosphate 86-89 HRas proto-oncogene, GTPase Homo sapiens 109-115 8019003-3 1994 In each system, the effects of H-ras depend on guanosine triphosphate and appear to be mediated through the H-ras effector binding region. Guanosine Triphosphate 47-69 HRas proto-oncogene, GTPase Homo sapiens 31-36 8195713-8 1994 Thus, the p210bcr/abl-dependent regulation of p120GAP activity is responsible, in part, for the maintenance of p21ras in the active GTP-bound form, a crucial requirement for CML cell proliferation. Guanosine Triphosphate 132-135 HRas proto-oncogene, GTPase Homo sapiens 111-117 7819259-6 1995 The Ran(T24N) mutant, which is analogous to the S17N mutant of p21ras, has decreased relative affinities for both GDP/GTP and favors GDP binding. Guanosine Triphosphate 118-121 HRas proto-oncogene, GTPase Homo sapiens 63-69 7926013-3 1994 In addition EGF induces stable association of the GTP-ase activating protein of p21ras to the p190 protein and to a 62 mol.wt. Guanosine Triphosphate 50-53 HRas proto-oncogene, GTPase Homo sapiens 80-86 8073283-1 1994 Mechanisms of guanosine triphosphate (GTP) hydrolysis by members of the G protein alpha subunit-p21ras superfamily of guanosine triphosphatases have been studied extensively but have not been well understood. Guanosine Triphosphate 14-36 HRas proto-oncogene, GTPase Homo sapiens 96-102 8073283-1 1994 Mechanisms of guanosine triphosphate (GTP) hydrolysis by members of the G protein alpha subunit-p21ras superfamily of guanosine triphosphatases have been studied extensively but have not been well understood. Guanosine Triphosphate 38-41 HRas proto-oncogene, GTPase Homo sapiens 96-102 15299412-1 1994 The parameters affecting the crystal quality of complexes between p21(H-ras) and caged GTP have been investigated. Guanosine Triphosphate 87-90 HRas proto-oncogene, GTPase Homo sapiens 70-75 8144662-0 1994 Shc is the predominant signaling molecule coupling insulin receptors to activation of guanine nucleotide releasing factor and p21ras-GTP formation. Guanosine Triphosphate 133-136 HRas proto-oncogene, GTPase Homo sapiens 126-132 8144662-2 1994 We investigated the relative role of IRS-1 and She in insulin activation of guanine nucleotide releasing factor (GNRF) and p21ras-GTP formation. Guanosine Triphosphate 130-133 HRas proto-oncogene, GTPase Homo sapiens 123-129 8144662-7 1994 In addition, the kinetics of insulin-stimulated GNRF activity and p21ras-GTP formation corresponded more closely to the time course of Shc phosphorylation than to the kinetics of IRS-1 phosphorylation. Guanosine Triphosphate 73-76 HRas proto-oncogene, GTPase Homo sapiens 66-72 8144662-9 1994 Thus, although both IRS-1 and Shc associate with Grb2, the current results indicate that Shc plays a more important role than IRS-1 in insulin stimulation of GNRF activity and subsequent p21ras-GTP formation. Guanosine Triphosphate 194-197 HRas proto-oncogene, GTPase Homo sapiens 187-193 8136358-1 1994 The active GTP-bound form of p21ras is converted to the biologically inactive GDP-bound form by enzymatic hydrolysis and this function serves to regulate the wild-type ras protein. Guanosine Triphosphate 11-14 HRas proto-oncogene, GTPase Homo sapiens 29-35 8137813-4 1994 The Q79L mutant of rab5, analogous with the activating Q61L mutant of p21-ras, was found to have a strongly decreased intrinsic GTPase activity and was, unlike wild-type rab5, found mainly in the GTP-bound form in vivo. Guanosine Triphosphate 128-131 HRas proto-oncogene, GTPase Homo sapiens 70-77 7787254-1 1994 Substitution of asparagine for serine at position 17 of human H-ras results in an impaired GTP-binding activity, causing the mutant Ras protein to be locked in a constitutively inactive GDP-bound state. Guanosine Triphosphate 91-94 HRas proto-oncogene, GTPase Homo sapiens 62-67 8338834-0 1993 An NMR comparison of the changes produced by different guanosine 5"-triphosphate analogs in wild-type and oncogenic mutant p21ras. Guanosine Triphosphate 55-80 HRas proto-oncogene, GTPase Homo sapiens 123-129 8257693-1 1993 The solution dynamics of normal and transforming p21ras proteins in both the GTP- and GDP-bound forms were examined with time-resolved fluorescence spectroscopy. Guanosine Triphosphate 77-80 HRas proto-oncogene, GTPase Homo sapiens 49-55 8245773-6 1993 Stimulation of MO7 cells with hematopoietic growth factors increased the expression of GAP as well as the levels of active GTP-bound p21ras. Guanosine Triphosphate 123-126 HRas proto-oncogene, GTPase Homo sapiens 133-139 8496156-1 1993 Essential role of Arg-903 of GAP in activation of GTP hydrolysis on p21ras. Guanosine Triphosphate 50-53 HRas proto-oncogene, GTPase Homo sapiens 68-74 8496156-11 1993 These data suggest a direct role for this residue in catalyzing GTP hydrolysis on p21ras, possibly by contributing a catalytic group to the p21 active site. Guanosine Triphosphate 64-67 HRas proto-oncogene, GTPase Homo sapiens 82-88 8407889-0 1993 Stimulation of tyrosine phosphorylation and accumulation of GTP-bound p21ras upon antibody-mediated alpha 2 beta 1 integrin activation in T-lymphoblastic cells. Guanosine Triphosphate 60-63 HRas proto-oncogene, GTPase Homo sapiens 70-76 8407889-3 1993 We report here that the ligation of alpha 2 beta 1 integrin by collagen-adhesion stimulatory anti-alpha 2 and anti-beta 1 antibodies resulted in the accumulation of p21ras in the active GTP-bound state in Jurkat T-lymphoblastoid cells. Guanosine Triphosphate 186-189 HRas proto-oncogene, GTPase Homo sapiens 165-171 8376929-1 1993 It has previously been shown in T cells that stimulation of protein kinase C (PKC) or the T cell antigen receptor (TCR) induces the rapid accumulation of the active guanosine triphosphate-bound form of p21ras. Guanosine Triphosphate 165-187 HRas proto-oncogene, GTPase Homo sapiens 202-208 8338834-8 1993 Thus, the two GTP analogs have similar effects on the spectrum of p21ras, suggesting that the effects are due to features common to both analogs. Guanosine Triphosphate 14-17 HRas proto-oncogene, GTPase Homo sapiens 66-72 8338834-13 1993 In (G12D)p21ras, replacement of GDP by GTP gamma S causes the resonances of glycines 10, 13, 15, 60, and 75 and isoleucine 21 and four others to shift from their GDP-specific positions. Guanosine Triphosphate 39-42 HRas proto-oncogene, GTPase Homo sapiens 9-15 8388384-1 1993 Insulin activates the ras proto-oncogene product p21ras (Ras) by stimulating conversion of the inactive GDP-bound form of Ras to the active GTP-bound form. Guanosine Triphosphate 140-143 HRas proto-oncogene, GTPase Homo sapiens 49-55 8486615-4 1993 These two regions change conformation on GTP binding by p21ras and, accordingly, both GAP binding and Ras biological activity are GTP-dependent processes. Guanosine Triphosphate 41-44 HRas proto-oncogene, GTPase Homo sapiens 56-62 8486615-4 1993 These two regions change conformation on GTP binding by p21ras and, accordingly, both GAP binding and Ras biological activity are GTP-dependent processes. Guanosine Triphosphate 130-133 HRas proto-oncogene, GTPase Homo sapiens 56-62 8486615-6 1993 On the other hand, the SDC25 exchange factor appears to promote dissociation of both GTP and GDP from p21ras, suggesting that the overall conformation of the switch 1 and 2 regions may not be important for recognition by SDC25. Guanosine Triphosphate 85-88 HRas proto-oncogene, GTPase Homo sapiens 102-108 8386636-0 1993 Nucleotide binding and GTP hydrolysis by the 21-kDa product of the c-H-ras gene as monitored by proton-NMR spectroscopy. Guanosine Triphosphate 23-26 HRas proto-oncogene, GTPase Homo sapiens 67-74 8386636-1 1993 Proton-NMR signals in the downfield region (below approximately 10 ppm) have been shown to provide a useful spectroscopic window to monitor the binding of guanine nucleotides to the active site of GTP/GDP-binding proteins via H-bonds, as specified here by the 21-kDa product of the c-H-ras gene (p21). Guanosine Triphosphate 197-200 HRas proto-oncogene, GTPase Homo sapiens 282-289 8444185-3 1993 Maximal activation of the receptor converts up to 65% of cellular p21ras from the GDP form into the active GTP-bound state. Guanosine Triphosphate 107-110 HRas proto-oncogene, GTPase Homo sapiens 66-72 8338834-1 1993 We have used nuclear magnetic resonance spectroscopy to compare the conformational changes produced by replacement of bound GDP by the GTP analogs guanosine 5"-O-(3-thiotriphosphate) (GTP gamma S) and guanylyl (beta, gamma-imido)diphosphate (GMPPNP) in wild-type p21ras as well as the oncogenic mutant (G12D)p21ras. Guanosine Triphosphate 135-138 HRas proto-oncogene, GTPase Homo sapiens 263-269 8338834-1 1993 We have used nuclear magnetic resonance spectroscopy to compare the conformational changes produced by replacement of bound GDP by the GTP analogs guanosine 5"-O-(3-thiotriphosphate) (GTP gamma S) and guanylyl (beta, gamma-imido)diphosphate (GMPPNP) in wild-type p21ras as well as the oncogenic mutant (G12D)p21ras. Guanosine Triphosphate 135-138 HRas proto-oncogene, GTPase Homo sapiens 308-314 8353139-7 1993 These oncogenes, which are frequently expressed in human malignancies, code for proteins (p21ras) that are locked in the activated GTP-bound state because their GTPase is refractory to the ras-specific GTPase activating protein (GAP). Guanosine Triphosphate 131-134 HRas proto-oncogene, GTPase Homo sapiens 90-96 8353139-8 1993 In other cases p21ras-GTP levels have been found to be elevated as a result of an increase in GDP/GTP exchange rate. Guanosine Triphosphate 22-25 HRas proto-oncogene, GTPase Homo sapiens 15-21 8353139-8 1993 In other cases p21ras-GTP levels have been found to be elevated as a result of an increase in GDP/GTP exchange rate. Guanosine Triphosphate 98-101 HRas proto-oncogene, GTPase Homo sapiens 15-21 8353139-10 1993 The protein encoded by NF1 contains a GAP homology region, binds p21ras-GTP, and stimulates the hydrolysis of p21ras-bound GTP. Guanosine Triphosphate 72-75 HRas proto-oncogene, GTPase Homo sapiens 65-71 8353139-12 1993 Elevated levels of these lipids may exert growth-stimulatory or perhaps tumor-promoting activity by increasing p21ras GTP. Guanosine Triphosphate 118-121 HRas proto-oncogene, GTPase Homo sapiens 111-117 8417322-1 1993 A number of growth factors, including insulin and epidermal growth factor (EGF), induce accumulation of the GTP-bound form of p21ras. Guanosine Triphosphate 108-111 HRas proto-oncogene, GTPase Homo sapiens 126-132 8423993-1 1993 The p21ras small GTP binding proteins participate in signal transduction from cell surface receptors and affect neoplastic transformation and development in many different cell types. Guanosine Triphosphate 17-20 HRas proto-oncogene, GTPase Homo sapiens 4-10 1321335-8 1992 Moreover, induction of fos promoter activity by GAP SH2-SH3 domains is increased severalfold after cotransfection of an activated mutant of p21ras, Ras(Leu-61), or insulin stimulation of A14 cells, both leading to an increase in the levels of GTP-bound p21ras. Guanosine Triphosphate 243-246 HRas proto-oncogene, GTPase Homo sapiens 140-146 1420142-0 1992 NMR studies of the conformational change in human N-p21ras produced by replacement of bound GDP with the GTP analog GTP gamma S. 1H-Detected 15N-edited NMR in solution was used to study the conformational differences between the GDP- and GTP gamma S-bound forms of human N-p21ras. Guanosine Triphosphate 105-108 HRas proto-oncogene, GTPase Homo sapiens 52-58 1420142-0 1992 NMR studies of the conformational change in human N-p21ras produced by replacement of bound GDP with the GTP analog GTP gamma S. 1H-Detected 15N-edited NMR in solution was used to study the conformational differences between the GDP- and GTP gamma S-bound forms of human N-p21ras. Guanosine Triphosphate 116-119 HRas proto-oncogene, GTPase Homo sapiens 52-58 1420142-0 1992 NMR studies of the conformational change in human N-p21ras produced by replacement of bound GDP with the GTP analog GTP gamma S. 1H-Detected 15N-edited NMR in solution was used to study the conformational differences between the GDP- and GTP gamma S-bound forms of human N-p21ras. Guanosine Triphosphate 116-119 HRas proto-oncogene, GTPase Homo sapiens 52-58 1420142-3 1992 When GTP gamma S replaced GDP in the active site of p21ras, only 5 of the 14 glycine amide resonances show major shifts, indicating that the conformational effects are fairly localized. Guanosine Triphosphate 5-8 HRas proto-oncogene, GTPase Homo sapiens 52-58 1445214-1 1992 The mechanism of GTPase-activating protein (GAP) activation of p21ras GTP hydrolysis has been investigated by measuring the kinetics of release of Pi during the hydrolysis. Guanosine Triphosphate 17-20 HRas proto-oncogene, GTPase Homo sapiens 63-69 1445214-8 1992 This phosphorolysis gives an absorbance increase at 360 nm, so that when the reaction is coupled to GTP hydrolysis, the change in absorbance gives the total amount of Pi released from the p21ras. Guanosine Triphosphate 100-103 HRas proto-oncogene, GTPase Homo sapiens 188-194 1321335-8 1992 Moreover, induction of fos promoter activity by GAP SH2-SH3 domains is increased severalfold after cotransfection of an activated mutant of p21ras, Ras(Leu-61), or insulin stimulation of A14 cells, both leading to an increase in the levels of GTP-bound p21ras. Guanosine Triphosphate 243-246 HRas proto-oncogene, GTPase Homo sapiens 253-259 1620132-1 1992 T-lymphocyte activation via the antigen receptor complex (TCR) results in accumulation of p21ras in the active GTP-bound state. Guanosine Triphosphate 111-114 HRas proto-oncogene, GTPase Homo sapiens 90-96 1421163-1 1992 The three-dimensional structure of the H-ras oncogene product p21 has been determined in both its active, GTP-bound and its inactive, GDP-bound forms. Guanosine Triphosphate 106-109 HRas proto-oncogene, GTPase Homo sapiens 39-44 1620132-5 1992 Thus, in the absence of PKC stimulation, the TCR was still able to induce accumulation of p21ras-GTP complexes, and this stimulation correlated with an inactivation of p21ras GTPase-activating proteins. Guanosine Triphosphate 97-100 HRas proto-oncogene, GTPase Homo sapiens 90-96 1547789-2 1992 To test the method we first demonstrated that p21ras and other classical GTP binding proteins could be labeled in a GTP-specific manner. Guanosine Triphosphate 73-76 HRas proto-oncogene, GTPase Homo sapiens 46-52 1608472-2 1992 Several of these growth factors also activate the ras proto-oncogene product, p21ras (Ras), by stimulating the conversion of the inactive GDP-bound form of Ras to the active GTP-bound form. Guanosine Triphosphate 174-177 HRas proto-oncogene, GTPase Homo sapiens 78-84 1599919-0 1992 Simulation of the solution structure of the H-ras p21-GTP complex. Guanosine Triphosphate 54-57 HRas proto-oncogene, GTPase Homo sapiens 44-49 1599919-1 1992 An unconstrained simulation of the GTP-bound form of the H-ras protein p21 is performed in an aqueous environment with charge-neutralizing counterions. Guanosine Triphosphate 35-38 HRas proto-oncogene, GTPase Homo sapiens 57-62 1620552-3 1992 For this purpose, cytosolic extracts were incubated with recombinant human p21ras complexed to [gamma-32P]GTP and the time-dependent decrease in p21ras bound radioactivity was measured. Guanosine Triphosphate 106-109 HRas proto-oncogene, GTPase Homo sapiens 75-81 1568246-4 1992 Although the p21ras proteins isolated from the tumor cells had normal (nonmutant) biochemical properties in vitro, they displayed elevated levels of bound GTP in vivo. Guanosine Triphosphate 155-158 HRas proto-oncogene, GTPase Homo sapiens 13-19 1568246-6 1992 Introduction of the catalytic region of GAP into this line resulted in morphological reversion and lower in vivo GTP binding by endogenous p21ras. Guanosine Triphosphate 113-116 HRas proto-oncogene, GTPase Homo sapiens 139-145 1568247-2 1992 Since p21ras.GTP is a major regulator of growth and differentiation, mutant neurofibromins resulting from somatic mutations in the NF1 gene might interfere with ras signaling pathways and contribute to the development of tumors. Guanosine Triphosphate 13-16 HRas proto-oncogene, GTPase Homo sapiens 6-12 1565661-0 1992 X-ray crystal structures of transforming p21 ras mutants suggest a transition-state stabilization mechanism for GTP hydrolysis. Guanosine Triphosphate 112-115 HRas proto-oncogene, GTPase Homo sapiens 41-48 1544886-4 1992 Here we show that both TGF beta 1 and TGF beta 2 (5 ng/ml) result in a rapid (within 6 or 12 min, respectively) stimulation of GTP bound to p21ras in TGF beta-sensitive intestinal epithelial cells. Guanosine Triphosphate 127-130 HRas proto-oncogene, GTPase Homo sapiens 140-146 1544886-5 1992 Further, the CCL64 epithelial cell line, extremely sensitive to growth inhibition by TGF beta, displayed a concentration-dependent increase in GTP bound to p21ras by TGF beta 1 and a rapid activation of p21ras by TGF beta 2. Guanosine Triphosphate 143-146 HRas proto-oncogene, GTPase Homo sapiens 156-162 1537820-1 1992 Antigen triggering of the T-cell receptor results in an accumulation of activated GTP-bound p21ras protein. Guanosine Triphosphate 82-85 HRas proto-oncogene, GTPase Homo sapiens 92-98 1547491-7 1992 In a three-dimensional G alpha model, based on the structure of p21ras, the effector-activating residues of alpha S form a surface on the membrane-facing side of the molecule; this surface includes a region that changes conformation upon binding GTP. Guanosine Triphosphate 246-249 HRas proto-oncogene, GTPase Homo sapiens 64-70 1547789-2 1992 To test the method we first demonstrated that p21ras and other classical GTP binding proteins could be labeled in a GTP-specific manner. Guanosine Triphosphate 116-119 HRas proto-oncogene, GTPase Homo sapiens 46-52 1371879-1 1992 Products of the ras gene family, termed p21ras, are GTP-binding proteins that have been implicated in signal transduction via receptors encoding tyrosine kinase domains. Guanosine Triphosphate 52-55 HRas proto-oncogene, GTPase Homo sapiens 40-46 1741165-7 1992 In vivo guanine nucleotide binding to p21ras in the revertant cell lines demonstrated binding of both GTP and GDP, indicating that reversion to the non-transformed phenotype was not due to inability of p21ras to bind GTP. Guanosine Triphosphate 102-105 HRas proto-oncogene, GTPase Homo sapiens 38-44 1740442-1 1992 p21ras and several other ras-related GTP-binding proteins are modified post-translationally by addition of 15-carbon farnesyl or 20-carbon geranylgeranyl isoprenoids to cysteines within a conserved carboxyl-terminal sequence motif, Caa(M/S/L), where a is an aliphatic amino acid. Guanosine Triphosphate 37-40 HRas proto-oncogene, GTPase Homo sapiens 0-6 1633420-2 1992 Regulation of p21ras is achieved by GTPase activating proteins, which control the rate of hydrolysis of GTP to GDP, and also by GDP dissociation stimulators, which catalyze the exchange of guanine nucleotides. Guanosine Triphosphate 36-39 HRas proto-oncogene, GTPase Homo sapiens 14-20 1938104-1 1991 Amino acid sequence homology between the GTPase Activating Protein (GAP) and the GTP-binding regulatory protein, Gs alpha, suggests that a specific region of GAP primary structure (residues 891-898) may be involved in its stimulation of p21ras GTP hydrolytic activity (McCormick, F. [1989] Nature 340, 678-679). Guanosine Triphosphate 41-44 HRas proto-oncogene, GTPase Homo sapiens 237-243 1925604-1 1991 The guanosine triphosphate (GTP)-binding proteins include signal-transducing heterotrimeric G proteins (for example, Gs, Gi), smaller GTP-binding proteins that function in protein sorting, and the oncogenic protein p21ras. Guanosine Triphosphate 28-31 HRas proto-oncogene, GTPase Homo sapiens 215-221 1569084-3 1992 We found that stimulation of HEL cells with erythropoietin induces a 5-fold increase in the amount of GTP bound to the endogenous p21ras. Guanosine Triphosphate 102-105 HRas proto-oncogene, GTPase Homo sapiens 130-136 1569084-6 1992 Moreover, inhibition of tyrosine kinases by genistein totally prevents the erythropoietin-induced accumulation of a p21ras.GTP complex. Guanosine Triphosphate 123-126 HRas proto-oncogene, GTPase Homo sapiens 116-122 1569084-8 1992 Furthermore, the ability of a lysate from erythropoietin-stimulated HEL cells to induce in vitro hydrolysis of GTP bound to p21ras was strongly reduced. Guanosine Triphosphate 111-114 HRas proto-oncogene, GTPase Homo sapiens 124-130 1569084-9 1992 These results demonstrate that activation of p21ras is an early event in the erythropoietin signal transduction pathway, and they suggest that accumulation of the p21ras.GTP complex may be triggered by inhibition of GTPase-activating protein activity. Guanosine Triphosphate 170-173 HRas proto-oncogene, GTPase Homo sapiens 45-51 1569084-9 1992 These results demonstrate that activation of p21ras is an early event in the erythropoietin signal transduction pathway, and they suggest that accumulation of the p21ras.GTP complex may be triggered by inhibition of GTPase-activating protein activity. Guanosine Triphosphate 170-173 HRas proto-oncogene, GTPase Homo sapiens 163-169 1939160-1 1991 Insulin treatment of fibroblasts overexpressing the insulin receptor causes a rapid accumulation of the GTP-bound form of p21ras. Guanosine Triphosphate 104-107 HRas proto-oncogene, GTPase Homo sapiens 122-128 1820685-2 1991 The activity of p21ras is determined by the concentration of GTP-p21ras, which is tightly regulated by a complex array of positive and negative control mechanisms. Guanosine Triphosphate 61-64 HRas proto-oncogene, GTPase Homo sapiens 16-22 1820685-2 1991 The activity of p21ras is determined by the concentration of GTP-p21ras, which is tightly regulated by a complex array of positive and negative control mechanisms. Guanosine Triphosphate 61-64 HRas proto-oncogene, GTPase Homo sapiens 65-71 1820685-3 1991 GAP and NF1 can negatively regulate p21ras activity by stimulating hydrolysis of GTP bound to p21ras. Guanosine Triphosphate 81-84 HRas proto-oncogene, GTPase Homo sapiens 36-42 1820685-3 1991 GAP and NF1 can negatively regulate p21ras activity by stimulating hydrolysis of GTP bound to p21ras. Guanosine Triphosphate 81-84 HRas proto-oncogene, GTPase Homo sapiens 94-100 1894647-10 1991 Inhibition of isoprenylation of proteins such as p21ras and other small GTP-binding proteins would alter their intracellular localization and, hence, disrupt their biological activity. Guanosine Triphosphate 72-75 HRas proto-oncogene, GTPase Homo sapiens 49-55 1938104-1 1991 Amino acid sequence homology between the GTPase Activating Protein (GAP) and the GTP-binding regulatory protein, Gs alpha, suggests that a specific region of GAP primary structure (residues 891-898) may be involved in its stimulation of p21ras GTP hydrolytic activity (McCormick, F. [1989] Nature 340, 678-679). Guanosine Triphosphate 81-84 HRas proto-oncogene, GTPase Homo sapiens 237-243 1904555-1 1991 The ras-encoded p21ras proteins bind GTP very tightly, but catalyse hydrolysis to GDP very slowly. Guanosine Triphosphate 37-40 HRas proto-oncogene, GTPase Homo sapiens 16-22 1773783-1 1991 The three-dimensional structure of the active guanosine triphosphate (GTP)-analogue-containing complex of the H-ras-encoded p21 has been determined. Guanosine Triphosphate 46-68 HRas proto-oncogene, GTPase Homo sapiens 110-115 1772429-0 1991 Low molecular weight GTP-binding proteins in hepatocytes and an assessment of the role of p21ras proteins in the activation of phospholipase D. A GTP-binding protein with an apparent molecular weight of 25 kDa was detected in hepatocyte extracts using SDS-PAGE and [alpha-32P]GTP. Guanosine Triphosphate 146-149 HRas proto-oncogene, GTPase Homo sapiens 90-96 1772429-0 1991 Low molecular weight GTP-binding proteins in hepatocytes and an assessment of the role of p21ras proteins in the activation of phospholipase D. A GTP-binding protein with an apparent molecular weight of 25 kDa was detected in hepatocyte extracts using SDS-PAGE and [alpha-32P]GTP. Guanosine Triphosphate 146-149 HRas proto-oncogene, GTPase Homo sapiens 90-96 1773783-1 1991 The three-dimensional structure of the active guanosine triphosphate (GTP)-analogue-containing complex of the H-ras-encoded p21 has been determined. Guanosine Triphosphate 70-73 HRas proto-oncogene, GTPase Homo sapiens 110-115 1703633-1 1991 GTPase-activating protein (GAP) is a cytosolic protein that stimulates the rate of hydrolysis of GTP (GTP to GDP) bound to normal p21ras, but does not catalyze the hydrolysis of GTP bound to oncogenic, activated forms of the ras protein. Guanosine Triphosphate 0-3 HRas proto-oncogene, GTPase Homo sapiens 130-136 1674518-3 1991 The activation state of p21ras is controlled by GTP levels on p21ras. Guanosine Triphosphate 48-51 HRas proto-oncogene, GTPase Homo sapiens 24-30 1674518-3 1991 The activation state of p21ras is controlled by GTP levels on p21ras. Guanosine Triphosphate 48-51 HRas proto-oncogene, GTPase Homo sapiens 62-68 1674518-4 1991 In T cells stimulation of protein kinase C is able to induce an accumulation of "active" p21ras-GTP complexes due to an inhibitory effect of protein kinase C stimulation on the intrinsic GTPase activity of p21ras. Guanosine Triphosphate 96-99 HRas proto-oncogene, GTPase Homo sapiens 89-95 1674518-4 1991 In T cells stimulation of protein kinase C is able to induce an accumulation of "active" p21ras-GTP complexes due to an inhibitory effect of protein kinase C stimulation on the intrinsic GTPase activity of p21ras. Guanosine Triphosphate 96-99 HRas proto-oncogene, GTPase Homo sapiens 206-212 1674518-6 1991 In the present report, we demonstrate that the TCR/CD3 complex and the CD2 Ag control the accumulation of p21ras-GTP complexes via a regulatory effect on p21ras GTPase activity. Guanosine Triphosphate 113-116 HRas proto-oncogene, GTPase Homo sapiens 106-112 1850098-1 1991 GTPase-activating protein (GAP) stimulates the ability of p21ras to hydrolyze GTP to GDP. Guanosine Triphosphate 0-3 HRas proto-oncogene, GTPase Homo sapiens 58-64 1703633-1 1991 GTPase-activating protein (GAP) is a cytosolic protein that stimulates the rate of hydrolysis of GTP (GTP to GDP) bound to normal p21ras, but does not catalyze the hydrolysis of GTP bound to oncogenic, activated forms of the ras protein. Guanosine Triphosphate 97-100 HRas proto-oncogene, GTPase Homo sapiens 130-136 1703633-1 1991 GTPase-activating protein (GAP) is a cytosolic protein that stimulates the rate of hydrolysis of GTP (GTP to GDP) bound to normal p21ras, but does not catalyze the hydrolysis of GTP bound to oncogenic, activated forms of the ras protein. Guanosine Triphosphate 97-100 HRas proto-oncogene, GTPase Homo sapiens 130-136 2146678-0 1990 Accumulation of p21ras.GTP in response to stimulation with epidermal growth factor and oncogene products with tyrosine kinase activity. Guanosine Triphosphate 23-26 HRas proto-oncogene, GTPase Homo sapiens 16-22 35324017-0 2022 Conformations and binding pockets of HRas and its guanine nucleotide exchange factors complexes in the guanosine triphosphate exchange process. Guanosine Triphosphate 103-125 HRas proto-oncogene, GTPase Homo sapiens 37-41 2196171-0 1990 Refined crystal structure of the triphosphate conformation of H-ras p21 at 1.35 A resolution: implications for the mechanism of GTP hydrolysis. Guanosine Triphosphate 128-131 HRas proto-oncogene, GTPase Homo sapiens 62-67 2196171-1 1990 The crystal structure of the H-ras oncogene protein p21 complexed to the slowly hydrolysing GTP analogue GppNp has been determined at 1.35 A resolution. Guanosine Triphosphate 92-95 HRas proto-oncogene, GTPase Homo sapiens 29-34 2169290-3 1990 We demonstrate that both the proto-oncogenic and the oncogenic form of H-ras proteins stimulate phospholipase C activity only when coupled to non-hydrolysable analogues of GTP. Guanosine Triphosphate 172-175 HRas proto-oncogene, GTPase Homo sapiens 71-76 2105317-12 1990 The observed isoprenoid-dependent carboxyl methylation of a group of 21-26-kDa proteins suggests that the low molecular mass GTP-binding proteins may undergo a series of post-translational C-terminal cysteine modifications (i.e. farnesylation, carboxyl methylation) analogous to those recently elucidated for p21ras. Guanosine Triphosphate 125-128 HRas proto-oncogene, GTPase Homo sapiens 309-315 2119552-1 1990 Structural, biochemical and molecular genetic studies of EF-Tu, p21ras and alpha s have begun to reveal the inner workings of the molecular machine used by these and other GTP-binding proteins. Guanosine Triphosphate 172-175 HRas proto-oncogene, GTPase Homo sapiens 64-70 2119552-2 1990 Further understanding of this molecular machine will ultimately come from crystal structures of the G protein alpha chains as well as from crystal structures of the GTP-bound forms of p21ras and EF-Tu. Guanosine Triphosphate 165-168 HRas proto-oncogene, GTPase Homo sapiens 184-190 35462078-8 2022 Interestingly, we found two Arginine fingers R68 and R149 that directly interact with the beta-phosphate of the GTP bound in KRas, in a manner similar to what is observed in a crystal structure of GAP-HRas complex, which can facilitate the GPT hydrolysis via the Arginine finger of GTPase-activating protein (GAP). Guanosine Triphosphate 112-115 HRas proto-oncogene, GTPase Homo sapiens 201-205 35459782-6 2022 Tipifarnib reduced HRAS processing, and plasma membrane localization leading to decreased GTP-bound HRAS and decreased signaling through RAS effector pathways. Guanosine Triphosphate 90-93 HRas proto-oncogene, GTPase Homo sapiens 100-104 2501306-7 1989 The homology (approximately 30%) between these rab proteins and p21ras is restricted to the four conserved domains involved in the GTP/GDP binding. Guanosine Triphosphate 131-134 HRas proto-oncogene, GTPase Homo sapiens 64-70 2549426-4 1989 This domain may serve as a built-in counter-part of the separate GTPase-activating proteins required for GTP hydrolysis by small GTP-binding proteins such as p21ras. Guanosine Triphosphate 65-68 HRas proto-oncogene, GTPase Homo sapiens 158-164 2549426-4 1989 This domain may serve as a built-in counter-part of the separate GTPase-activating proteins required for GTP hydrolysis by small GTP-binding proteins such as p21ras. Guanosine Triphosphate 105-108 HRas proto-oncogene, GTPase Homo sapiens 158-164 35202574-3 2022 Using X-ray crystallography, nuclear magnetic resonance spectroscopy, binding assays, and molecular dynamics on autophosphorylated mutants of H-RAS and K-RAS, we show that phosphoryl transfer from GTP requires dynamic movement of the switch II region and that autophosphorylation promotes nucleotide exchange by opening the active site and extracting the stabilizing Mg2+. Guanosine Triphosphate 197-200 HRas proto-oncogene, GTPase Homo sapiens 142-147 2502981-4 1989 On the contrary, both the amount of p21ras and its GTP-binding activity are low prior to emergence and rises afterwards. Guanosine Triphosphate 51-54 HRas proto-oncogene, GTPase Homo sapiens 36-42 2516316-1 1989 The functions of G proteins--like those of bacterial elongation factor (EF) Tu and the 21 kDa ras proteins (p21ras)--depend upon their abilities to bind and hydrolyze GTP and to assume different conformations in GTP- and GDP-bound states. Guanosine Triphosphate 167-170 HRas proto-oncogene, GTPase Homo sapiens 108-114 2516316-1 1989 The functions of G proteins--like those of bacterial elongation factor (EF) Tu and the 21 kDa ras proteins (p21ras)--depend upon their abilities to bind and hydrolyze GTP and to assume different conformations in GTP- and GDP-bound states. Guanosine Triphosphate 212-215 HRas proto-oncogene, GTPase Homo sapiens 108-114 2516316-2 1989 Similarities in function and amino acid sequence indicate that EF-Tu, p21ras, and G protein alpha-chains evolved from a primordial GTP-binding protein. Guanosine Triphosphate 131-134 HRas proto-oncogene, GTPase Homo sapiens 70-76 2516316-7 1989 A second class of GTPase inhibiting mutations in alpha s occurs in the codon for an Arg residue whose covalent modification by cholera toxin also inhibits GTP hydrolysis by alpha s. This Arg residue is located in a domain of alpha s not represented in EF-Tu or p21ras. Guanosine Triphosphate 18-21 HRas proto-oncogene, GTPase Homo sapiens 261-267 2516316-8 1989 We propose that this domain constitutes an intrinsic activator of GTP hydrolysis, and that it performs a function analogous to that performed for EF-Tu by the programmed ribosome and for p21ras by the recently discovered GTPase-activating protein. Guanosine Triphosphate 66-69 HRas proto-oncogene, GTPase Homo sapiens 187-193 2999765-5 1985 Immediately adjacent to this region is a small sequence of limited similarity that exists not only in EF-G, EF-Tu, and IF2 but also in the protooncogene c-Ha-ras-1 (from human bladder) and other GTP-binding proteins. Guanosine Triphosphate 195-198 HRas proto-oncogene, GTPase Homo sapiens 153-163 3045729-4 1988 The C-terminal cysteine involved in the membrane anchoring as well as the GTP binding regions of the p21 ras proteins are present in the rap proteins suggesting that these proteins could bind GTP/GDP and have a membrane localization. Guanosine Triphosphate 74-77 HRas proto-oncogene, GTPase Homo sapiens 101-108 3045729-4 1988 The C-terminal cysteine involved in the membrane anchoring as well as the GTP binding regions of the p21 ras proteins are present in the rap proteins suggesting that these proteins could bind GTP/GDP and have a membrane localization. Guanosine Triphosphate 192-195 HRas proto-oncogene, GTPase Homo sapiens 101-108 3077934-2 1988 The active form of the p21 ras proteins is the GTP bound state and oncogenic mutations result in the protein being constitutively in the GTP bound active state. Guanosine Triphosphate 47-50 HRas proto-oncogene, GTPase Homo sapiens 23-30 3077934-2 1988 The active form of the p21 ras proteins is the GTP bound state and oncogenic mutations result in the protein being constitutively in the GTP bound active state. Guanosine Triphosphate 137-140 HRas proto-oncogene, GTPase Homo sapiens 23-30 3077934-4 1988 To transduce a signal for proliferation and transformation the active GTP form of p21ras must interact with one or more cellular targets. Guanosine Triphosphate 70-73 HRas proto-oncogene, GTPase Homo sapiens 82-88 3308383-5 1987 This M.W 21,000 protein possessed the capability to bind with GTP, i.e. the character of P21ras. Guanosine Triphosphate 62-65 HRas proto-oncogene, GTPase Homo sapiens 89-95 3058913-1 1988 The ras oncogenes encode for GTP binding and GTPase active proteins of relative molecular mass 21,000 (p21ras) which are involved in the transduction of stimuli for cell proliferation. Guanosine Triphosphate 29-32 HRas proto-oncogene, GTPase Homo sapiens 103-109