PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 17222906-5 2007 In AML cells, with cooperating mutations, the expression of the neurofibromin GRD causes significant reductions of N- and K-Ras-GTP levels, which is not incompatible with AML cell survival, but which is strongly selected against due to suppression of proliferation. Guanosine Triphosphate 128-131 KRAS proto-oncogene, GTPase Homo sapiens 122-127 16103080-1 2005 Galectin-3 (Gal-3), a pleiotropic carbohydrate-binding protein, is a selective binding partner of activated K-Ras-GTP. Guanosine Triphosphate 114-117 KRAS proto-oncogene, GTPase Homo sapiens 108-113 16757312-3 2006 While characterizing the biochemical properties of several commonly detected K-Ras mutants, we made the unexpected observation that an activity in crude bacterial cell extracts was capable of stimulating the conversion of the oncogenic K-RasG13D mutant from a GTP-bound, active form to a GDP-bound, inactive form. Guanosine Triphosphate 260-263 KRAS proto-oncogene, GTPase Homo sapiens 77-82 17601930-6 2007 The F156L mutant K-Ras protein accumulated in the active, guanosine triphosphate-bound conformation and affected downstream signalling. Guanosine Triphosphate 58-80 KRAS proto-oncogene, GTPase Homo sapiens 17-22 16923573-0 2006 Detection of N-RAS and K-RAS in their active GTP-bound form in acute myeloid leukemia without activating RAS mutations. Guanosine Triphosphate 45-48 KRAS proto-oncogene, GTPase Homo sapiens 23-28 16923573-3 2006 Further analysis revealed the simultaneous presence of N-RAS and K-RAS proteins in the GTP-bound state in seven out of 10 AML samples. Guanosine Triphosphate 87-90 KRAS proto-oncogene, GTPase Homo sapiens 65-70 15205467-5 2004 Galectin-3 co-immunoprecipitated significantly better with K-Ras-GTP than with K-Ras-GDP, H-Ras, or N-Ras and colocalized with green fluorescent protein-K-Ras(G12V), not with green fluorescent protein-H-Ras(G12V), in the cell membrane. Guanosine Triphosphate 65-68 KRAS proto-oncogene, GTPase Homo sapiens 59-64 15574778-7 2004 RASSF4 binds directly to activated K-Ras in a GTP-dependent manner via the effector domain, thus exhibiting the basic properties of a Ras effector. Guanosine Triphosphate 46-49 KRAS proto-oncogene, GTPase Homo sapiens 35-40 15205467-6 2004 Co-transfectants of K-Ras/galectin-3, but not of H-Ras/galectin-3, exhibited enhanced and prolonged epidermal growth factor-stimulated increases in Ras-GTP, Raf-1 activity, and PI3-K activity. Guanosine Triphosphate 152-155 KRAS proto-oncogene, GTPase Homo sapiens 20-25 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 KRAS proto-oncogene, GTPase Homo sapiens 76-83 15215250-1 2004 Aldosterone induces expression and activation of the GTP-dependent signaling switch K-Ras. Guanosine Triphosphate 53-56 KRAS proto-oncogene, GTPase Homo sapiens 84-89 15215250-4 2004 We demonstrate here that K-Ras activates human ENaC reconstituted in Chinese hamster ovary cells in a GTP-dependent manner. Guanosine Triphosphate 102-105 KRAS proto-oncogene, GTPase Homo sapiens 25-30 14506738-7 2003 Mutant K-ras genes were expressed at high levels in E. coli and the mutant K-ras proteins were shown to be functional with respect to their well-known specific, high-affinity, GDP/GTP binding. Guanosine Triphosphate 180-183 KRAS proto-oncogene, GTPase Homo sapiens 7-12 14506738-7 2003 Mutant K-ras genes were expressed at high levels in E. coli and the mutant K-ras proteins were shown to be functional with respect to their well-known specific, high-affinity, GDP/GTP binding. Guanosine Triphosphate 180-183 KRAS proto-oncogene, GTPase Homo sapiens 75-80 12732644-8 2003 RASSF2 binds directly to K-Ras in a GTP-dependent manner via the Ras effector domain. Guanosine Triphosphate 36-39 KRAS proto-oncogene, GTPase Homo sapiens 25-30 12354753-3 2002 In all three cell types, total K-ras p21 increased 2- to 4-fold at confluence, and active K-ras p21-GTP increased 10- to 200-fold. Guanosine Triphosphate 100-103 KRAS proto-oncogene, GTPase Homo sapiens 90-95 12354753-4 2002 It was estimated that 0.03% of total K-ras p21 was in the active GTP-bound state at 50% confluence, compared with 1.4% at postconfluence. Guanosine Triphosphate 65-68 KRAS proto-oncogene, GTPase Homo sapiens 37-42 10737386-4 2000 Mutant K-Ras genes were expressed at high levels in Escherichia coli and the resultant K-Ras proteins were shown to be functional with respect to their well-known specific, high-affinity, GDP/GTP binding. Guanosine Triphosphate 192-195 KRAS proto-oncogene, GTPase Homo sapiens 7-12 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 KRAS proto-oncogene, GTPase Homo sapiens 10-15 11799108-6 2002 We generated cytosolic GTP-bound H-, N-, and K-Ras, and we assessed their ability to inhibit Ras-induced phenotypes. Guanosine Triphosphate 23-26 KRAS proto-oncogene, GTPase Homo sapiens 45-50 10737386-4 2000 Mutant K-Ras genes were expressed at high levels in Escherichia coli and the resultant K-Ras proteins were shown to be functional with respect to their well-known specific, high-affinity, GDP/GTP binding. Guanosine Triphosphate 192-195 KRAS proto-oncogene, GTPase Homo sapiens 87-92 8900189-1 1996 Smg GDS is a regulator having two activities on a group of small G proteins including the Rho and Rap1 family members and Ki-Ras; one is to stimulate their GDP/GTP exchange reactions, and the other is to inhibit their interactions with membranes. Guanosine Triphosphate 160-163 KRAS proto-oncogene, GTPase Homo sapiens 122-128 10624710-7 1999 Black and green tea extracts, GTP, and EGCG decreased the expression of the K-ras gene, as determined by reverse transcription-polymerase chain reaction. Guanosine Triphosphate 30-33 KRAS proto-oncogene, GTPase Homo sapiens 76-81 9657959-9 1998 Although the NS3 protein was able to utilize all four ribonucleoside triphosphates as its substrates, the NS3 protein showed a distinct preference for purine triphosphates (i.e., ATP and GTP). Guanosine Triphosphate 187-190 KRAS proto-oncogene, GTPase Homo sapiens 106-109 10522044-1 1999 BACKGROUND/AIMS: The Ki-ras gene located at 12p, encodes the GTP binding protein involving the signal transduction system and concerns cell proliferation and differentiation. Guanosine Triphosphate 61-64 KRAS proto-oncogene, GTPase Homo sapiens 21-27 9171352-6 1997 Ras was the only component in these membranes required for activation, as purified recombinant farnesylated K-Ras.GTP, but not non-farnesylated K-Ras.GTP or farnesylated K-Ras.GDP, was able to activate c-Raf-1 to the same degree as intact H-RasG12V membranes. Guanosine Triphosphate 114-117 KRAS proto-oncogene, GTPase Homo sapiens 108-113 8947526-10 1996 K-ras mutants had increased levels of ras-GTP compared to wild-type cell lines. Guanosine Triphosphate 42-45 KRAS proto-oncogene, GTPase Homo sapiens 0-5 8947526-13 1996 A positive correlation between the presence of K-ras mutation, increased ras-GTP level, and increased cell surface beta 1-6 N-linked carbohydrate exists in pancreatic cancer cell lines. Guanosine Triphosphate 77-80 KRAS proto-oncogene, GTPase Homo sapiens 47-52 9631088-4 1996 The local fluorescence enhancement method was used to study the membrane dissociation rate of GFP-tagged K-ras, a small GTP binding protein that localizes to plasma membranes by a farnesyl lipid group and a polybasic region. Guanosine Triphosphate 120-123 KRAS proto-oncogene, GTPase Homo sapiens 105-110 8195145-1 1994 We have previously shown that both Smg GDP dissociation stimulator (GDS) and mammalian Cdc25 (mCdc25) stimulate the GDP/GTP exchange reaction of Ki-Ras and that Smg GDS is active only on the post-translationally lipid-modified form of Ki-Ras, whereas mCdc25 is active on both the lipid-modified and unmodified forms but is more active on the lipid-modified form. Guanosine Triphosphate 120-123 KRAS proto-oncogene, GTPase Homo sapiens 145-151 8820445-6 1996 K-ras proteins are small (21-kd) proteins that normally serve as guanosine triphosphate (GTP)-regulated switches to control a diverse array of cellular signals that modulate highly regulated programs of proliferation, differentiation, and death. Guanosine Triphosphate 65-87 KRAS proto-oncogene, GTPase Homo sapiens 0-5 8820445-6 1996 K-ras proteins are small (21-kd) proteins that normally serve as guanosine triphosphate (GTP)-regulated switches to control a diverse array of cellular signals that modulate highly regulated programs of proliferation, differentiation, and death. Guanosine Triphosphate 89-92 KRAS proto-oncogene, GTPase Homo sapiens 0-5 7547927-1 1995 The small GTP-binding protein G25K and the protein K-Ras 4B contain prenyl groups (geranylgeranyl and farnesyl, respectively) that are thioether linked to a C-terminal cysteine which is methylated on its alpha-carboxyl group. Guanosine Triphosphate 10-13 KRAS proto-oncogene, GTPase Homo sapiens 51-59 8195145-1 1994 We have previously shown that both Smg GDP dissociation stimulator (GDS) and mammalian Cdc25 (mCdc25) stimulate the GDP/GTP exchange reaction of Ki-Ras and that Smg GDS is active only on the post-translationally lipid-modified form of Ki-Ras, whereas mCdc25 is active on both the lipid-modified and unmodified forms but is more active on the lipid-modified form. Guanosine Triphosphate 120-123 KRAS proto-oncogene, GTPase Homo sapiens 235-241 8195145-4 1994 In the presence of guanosine 5"-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. Guanosine Triphosphate 57-60 KRAS proto-oncogene, GTPase Homo sapiens 121-127 8195145-4 1994 In the presence of guanosine 5"-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. Guanosine Triphosphate 57-60 KRAS proto-oncogene, GTPase Homo sapiens 209-215 8195145-4 1994 In the presence of guanosine 5"-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. Guanosine Triphosphate 57-60 KRAS proto-oncogene, GTPase Homo sapiens 209-215 8195145-4 1994 In the presence of guanosine 5"-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. Guanosine Triphosphate 109-112 KRAS proto-oncogene, GTPase Homo sapiens 121-127 8195145-4 1994 In the presence of guanosine 5"-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. Guanosine Triphosphate 109-112 KRAS proto-oncogene, GTPase Homo sapiens 209-215 8195145-4 1994 In the presence of guanosine 5"-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. Guanosine Triphosphate 109-112 KRAS proto-oncogene, GTPase Homo sapiens 209-215 8195145-4 1994 In the presence of guanosine 5"-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. Guanosine Triphosphate 109-112 KRAS proto-oncogene, GTPase Homo sapiens 121-127 8195145-4 1994 In the presence of guanosine 5"-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. Guanosine Triphosphate 109-112 KRAS proto-oncogene, GTPase Homo sapiens 209-215 8195145-4 1994 In the presence of guanosine 5"-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. Guanosine Triphosphate 109-112 KRAS proto-oncogene, GTPase Homo sapiens 209-215 8195145-4 1994 In the presence of guanosine 5"-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. Guanosine Triphosphate 109-112 KRAS proto-oncogene, GTPase Homo sapiens 121-127 8195145-4 1994 In the presence of guanosine 5"-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. Guanosine Triphosphate 109-112 KRAS proto-oncogene, GTPase Homo sapiens 209-215 8195145-4 1994 In the presence of guanosine 5"-(3-O-thio) triphosphate (GTP gamma S), the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras was produced, whereas GTP gamma S induced the dissociation of mCdc25 from mCdc25-Ki-Ras complex, yielding GTP gamma S-Ki-Ras. Guanosine Triphosphate 109-112 KRAS proto-oncogene, GTPase Homo sapiens 209-215 8195145-6 1994 Moreover, Smg GDS translocated the GTP gamma S-bound form of membrane-bound Ki-Ras to the soluble fraction as the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras, whereas mCdc25 did not show this activity. Guanosine Triphosphate 35-38 KRAS proto-oncogene, GTPase Homo sapiens 76-82 8195145-6 1994 Moreover, Smg GDS translocated the GTP gamma S-bound form of membrane-bound Ki-Ras to the soluble fraction as the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras, whereas mCdc25 did not show this activity. Guanosine Triphosphate 35-38 KRAS proto-oncogene, GTPase Homo sapiens 160-166 8195145-6 1994 Moreover, Smg GDS translocated the GTP gamma S-bound form of membrane-bound Ki-Ras to the soluble fraction as the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras, whereas mCdc25 did not show this activity. Guanosine Triphosphate 148-151 KRAS proto-oncogene, GTPase Homo sapiens 76-82 8195145-6 1994 Moreover, Smg GDS translocated the GTP gamma S-bound form of membrane-bound Ki-Ras to the soluble fraction as the stable ternary complex of Smg GDS-GTP gamma S-Ki-Ras, whereas mCdc25 did not show this activity. Guanosine Triphosphate 148-151 KRAS proto-oncogene, GTPase Homo sapiens 160-166 34570515-0 2021 Conformational Fluctuations in GTP-Bound K-Ras: A Metadynamics Perspective with Harmonic Linear Discriminant Analysis. Guanosine Triphosphate 31-34 KRAS proto-oncogene, GTPase Homo sapiens 41-46 1501882-2 1992 The GDP/GTP exchange reaction of smg p21 is regulated by smg GDS, which is also active on Ki-ras p21 and rho p21. Guanosine Triphosphate 8-11 KRAS proto-oncogene, GTPase Homo sapiens 90-96 33034275-1 2022 K-Ras is a small GTPase and acts as a molecular switch by recruiting GEFs and GAPs, and alternates between the inert GDP-bound and the dynamic GTP-bound forms. Guanosine Triphosphate 17-20 KRAS proto-oncogene, GTPase Homo sapiens 0-5 33034275-5 2022 The docking of GTP with K-Ras was carried out using AutoDock4.2, followed by molecular dynamics simulations. Guanosine Triphosphate 15-18 KRAS proto-oncogene, GTPase Homo sapiens 24-29 34988297-1 2022 Oncogenic mutations in KRAS result in a constitutively active, GTP-bound form that in turn activates many proliferative pathways. Guanosine Triphosphate 63-66 KRAS proto-oncogene, GTPase Homo sapiens 23-27 34787842-2 2022 KRAS proteins form complexes with GTP and GDP to result in active and inactive conformations favouring interactions with different proteins. Guanosine Triphosphate 34-37 KRAS proto-oncogene, GTPase Homo sapiens 0-4 8117282-3 1994 The Ash-interacting proteins stimulated the GDP/GTP exchange reaction of Ki-Ras and Ha-Ras but not that of other small GTP-binding proteins including at least Rap1, RhoA, Rac1, and Rab3A. Guanosine Triphosphate 48-51 KRAS proto-oncogene, GTPase Homo sapiens 73-79 8117282-3 1994 The Ash-interacting proteins stimulated the GDP/GTP exchange reaction of Ki-Ras and Ha-Ras but not that of other small GTP-binding proteins including at least Rap1, RhoA, Rac1, and Rab3A. Guanosine Triphosphate 119-122 KRAS proto-oncogene, GTPase Homo sapiens 73-79 34920161-0 2022 In silico comparative analysis of KRAS mutations at codons 12 and 13: Structural modifications of P-Loop, switch I&II regions preventing GTP hydrolysis. Guanosine Triphosphate 137-140 KRAS proto-oncogene, GTPase Homo sapiens 34-38 34920161-5 2022 We used bioinformatics as a tool to analyze the KRAS protein"s GTP (guanosine triphosphate) binding dynamics when mutated. Guanosine Triphosphate 63-66 KRAS proto-oncogene, GTPase Homo sapiens 48-52 34920161-5 2022 We used bioinformatics as a tool to analyze the KRAS protein"s GTP (guanosine triphosphate) binding dynamics when mutated. Guanosine Triphosphate 68-90 KRAS proto-oncogene, GTPase Homo sapiens 48-52 34920161-6 2022 KRAS undergoes significant conformational changes, affecting GTP binding conformation within the active site pocket of KRAS due to high torsional strains, hydrophobicity, and altered Switch I and II regions. Guanosine Triphosphate 61-64 KRAS proto-oncogene, GTPase Homo sapiens 0-4 34920161-6 2022 KRAS undergoes significant conformational changes, affecting GTP binding conformation within the active site pocket of KRAS due to high torsional strains, hydrophobicity, and altered Switch I and II regions. Guanosine Triphosphate 61-64 KRAS proto-oncogene, GTPase Homo sapiens 119-123 34551282-5 2021 Insulin-induced KARATE assembly is controlled via phosphorylation of GTP-bound KRAS4B at S181 and GDP-bound RHOA at S188 by protein kinase A. Guanosine Triphosphate 69-72 KRAS proto-oncogene, GTPase Homo sapiens 79-85 34570515-8 2021 More precisely, we study the K-Ras protein bound to GTP, focusing on two flexible loops and on the region associated with oncogenic mutations. Guanosine Triphosphate 52-55 KRAS proto-oncogene, GTPase Homo sapiens 29-34 35631410-4 2022 A variety of novel small molecules that directly target KRAS are being developed, including covalent allosteric inhibitors for KRASG12C mutant, protein-protein interaction inhibitors that bind in the switch I/II pocket or the A59 site, and GTP-competitive inhibitors targeting the nucleotide-binding site. Guanosine Triphosphate 240-243 KRAS proto-oncogene, GTPase Homo sapiens 56-60 34625747-4 2021 Our starting point was an asymmetric guanosine triphosphate-mediated K-Ras dimer model, which we generated using unbiased molecular dynamics simulations and verified with mutagenesis experiments. Guanosine Triphosphate 37-59 KRAS proto-oncogene, GTPase Homo sapiens 69-74 34703570-2 2021 KRAS is a frequently mutated oncogene, and while it is well known that the most prevalent mutation, G12D, impairs GTP hydrolysis, thereby increasing KRAS activation, G12D has also been shown to enhance nanoclustering. Guanosine Triphosphate 114-117 KRAS proto-oncogene, GTPase Homo sapiens 149-153 34237589-5 2021 We found that the residues K42, I142, and L159 are the hotspots from water, including the K-Ras-GTP complex with the highest residue centrality analysis (RCA) Z-score. Guanosine Triphosphate 96-99 KRAS proto-oncogene, GTPase Homo sapiens 90-95 34703570-2 2021 KRAS is a frequently mutated oncogene, and while it is well known that the most prevalent mutation, G12D, impairs GTP hydrolysis, thereby increasing KRAS activation, G12D has also been shown to enhance nanoclustering. Guanosine Triphosphate 114-117 KRAS proto-oncogene, GTPase Homo sapiens 0-4 34347509-3 2021 The use of therapeutics in combination with KRAS inhibitors are expected to improve outcomes.Areas covered: This review describes the KRAS G12C mutation-specific inhibitors and the SOS1-targeting inhibitors that reduce the GTP- loading of wildtype and mutated KRAS. Guanosine Triphosphate 223-226 KRAS proto-oncogene, GTPase Homo sapiens 44-48 34347509-3 2021 The use of therapeutics in combination with KRAS inhibitors are expected to improve outcomes.Areas covered: This review describes the KRAS G12C mutation-specific inhibitors and the SOS1-targeting inhibitors that reduce the GTP- loading of wildtype and mutated KRAS. Guanosine Triphosphate 223-226 KRAS proto-oncogene, GTPase Homo sapiens 260-264 34345014-10 2021 Importantly, the upregulation of RNF141 increased GTP-bound KRAS, but its knockdown resulted in a reduction accordingly. Guanosine Triphosphate 50-53 KRAS proto-oncogene, GTPase Homo sapiens 60-64 35614853-11 2022 Using immunoprecipitation assays, we show that SmgGDS-558 binds the GTP-bound, GDP-bound, and nucleotide-free forms of farnesylated and fully processed KRas in cells, consistent with SmgGDS-558 not engaging the G-domain of KRas. Guanosine Triphosphate 68-71 KRAS proto-oncogene, GTPase Homo sapiens 152-156 35614853-11 2022 Using immunoprecipitation assays, we show that SmgGDS-558 binds the GTP-bound, GDP-bound, and nucleotide-free forms of farnesylated and fully processed KRas in cells, consistent with SmgGDS-558 not engaging the G-domain of KRas. Guanosine Triphosphate 68-71 KRAS proto-oncogene, GTPase Homo sapiens 223-227 35105836-9 2022 Using examples from published data we show that the all-atom GNM gives B-factors that are in better agreement with experiment, can explain effects of mutation on long range communication in PDZ domains and can predict effects of GDP and GTP binding on the dimerization of KRAS. Guanosine Triphosphate 237-240 KRAS proto-oncogene, GTPase Homo sapiens 272-276 35586192-0 2022 Free Energy Profiles Relating With Conformational Transition of the Switch Domains Induced by G12 Mutations in GTP-Bound KRAS. Guanosine Triphosphate 111-114 KRAS proto-oncogene, GTPase Homo sapiens 121-125 35586192-3 2022 Free energy landscapes suggest that G12C, G12D and G12R induce more energetic states compared to the GTP-bound WT KRAS and make the conformations of the switch domains more disordered, which disturbs bindings of KRAS to effectors. Guanosine Triphosphate 101-104 KRAS proto-oncogene, GTPase Homo sapiens 114-118 35586192-3 2022 Free energy landscapes suggest that G12C, G12D and G12R induce more energetic states compared to the GTP-bound WT KRAS and make the conformations of the switch domains more disordered, which disturbs bindings of KRAS to effectors. Guanosine Triphosphate 101-104 KRAS proto-oncogene, GTPase Homo sapiens 212-216 35158284-7 2022 Utilizing a KRAS-GTP pull-down assay, it was demonstrated that K20 decreased the active form of KRAS (KRAS-GTP) in NCI-H358 cells. Guanosine Triphosphate 17-20 KRAS proto-oncogene, GTPase Homo sapiens 12-16 35158284-7 2022 Utilizing a KRAS-GTP pull-down assay, it was demonstrated that K20 decreased the active form of KRAS (KRAS-GTP) in NCI-H358 cells. Guanosine Triphosphate 17-20 KRAS proto-oncogene, GTPase Homo sapiens 96-100 35158284-7 2022 Utilizing a KRAS-GTP pull-down assay, it was demonstrated that K20 decreased the active form of KRAS (KRAS-GTP) in NCI-H358 cells. Guanosine Triphosphate 17-20 KRAS proto-oncogene, GTPase Homo sapiens 102-106 35297922-0 2022 Identification of functional substates of KRas during GTP hydrolysis with enhanced sampling simulations. Guanosine Triphosphate 54-57 KRAS proto-oncogene, GTPase Homo sapiens 42-46 35297922-3 2022 In this work, we perform an extensive simulation analysis on the conformational landscape of KRas in its various chemical states during the GTP hydrolysis cycle: the reactant state KRasGTP Mg2+, the intermediate state KRasGDP Pi Mg2+ and the product state KRasGDP Mg2+. Guanosine Triphosphate 140-143 KRAS proto-oncogene, GTPase Homo sapiens 93-97 35297922-8 2022 Based on these results, some specific inhibition strategies for targeting the binding sites of the high-energy substates of KRas during GTP hydrolysis are discussed. Guanosine Triphosphate 136-139 KRAS proto-oncogene, GTPase Homo sapiens 124-128 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 KRAS proto-oncogene, GTPase Homo sapiens 125-129 35463958-3 2022 To address the mechanism underlying the long-range allosteric activation of the catalytic K-Ras4B by an additional allosteric GTP-Ras through SOS, we employed molecular dynamics simulation of the K-Ras4BG13D SOScat complex with and without an allosteric GTP-bound K-Ras4BG13D. Guanosine Triphosphate 126-129 KRAS proto-oncogene, GTPase Homo sapiens 90-97 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 KRAS proto-oncogene, GTPase Homo sapiens 152-157 35267628-1 2022 KRAS is the most frequently mutated oncogene in non-small cell lung cancers (NSCLC), with a frequency of around 30%, and encoding a GTPAse that cycles between active form (GTP-bound) to inactive form (GDP-bound). Guanosine Triphosphate 172-175 KRAS proto-oncogene, GTPase Homo sapiens 0-4 35267628-8 2022 Small molecules such as sotorasib are now the first targeted drugs for KRAS G12C mutation, preventing conversion of the mutant protein to GTP-bound active state. Guanosine Triphosphate 138-141 KRAS proto-oncogene, GTPase Homo sapiens 71-75 33744388-2 2021 Here, we developed a RT22-ep59 antibody (Ab) that directly targets the intracellularly activated GTP-bound form of oncogenic KRAS mutants after it is internalized into cytosol by endocytosis through tumor-associated receptor of extracellular epithelial cell adhesion molecule (EpCAM) and investigated its synergistic anticancer effects in the presence of gemcitabine in pancreatic cancer. Guanosine Triphosphate 97-100 KRAS proto-oncogene, GTPase Homo sapiens 125-129 35142321-0 2022 Predicting the conformational variability of oncogenic GTP-bound G12D mutated KRas-4B proteins at zwitterionic model cell membranes. Guanosine Triphosphate 55-58 KRAS proto-oncogene, GTPase Homo sapiens 78-85 35142321-6 2022 We tested the methodology using a G12D mutated GTP bound oncogenic KRas-4B protein located at the interface of a DOPC/DOPS/cholesterol model anionic cell membrane. Guanosine Triphosphate 47-50 KRAS proto-oncogene, GTPase Homo sapiens 67-74 35142321-9 2022 We have observed that GTP-binding to KRas-4B has huge influence on the stabilisation of the protein and it can potentially help to open Switch I/II druggable pockets, lowering energy barriers between stable states and resulting in cumulative conformers of KRas-4B. Guanosine Triphosphate 22-25 KRAS proto-oncogene, GTPase Homo sapiens 37-44 35142321-9 2022 We have observed that GTP-binding to KRas-4B has huge influence on the stabilisation of the protein and it can potentially help to open Switch I/II druggable pockets, lowering energy barriers between stable states and resulting in cumulative conformers of KRas-4B. Guanosine Triphosphate 22-25 KRAS proto-oncogene, GTPase Homo sapiens 256-263 35075146-3 2022 Our ITC results show that these inhibitors have similar binding affinity with both GDP-bound and GTP-bound KRAS(G12D), and our crystallographic studies reveal the structural basis of inhibitor binding-induced switch-II pocket in KRAS(G12D), experimentally confirming the formation of a salt bridge between the piperazine moiety of the inhibitors and the Asp12 residue of the mutant protein. Guanosine Triphosphate 97-100 KRAS proto-oncogene, GTPase Homo sapiens 107-111 35075146-3 2022 Our ITC results show that these inhibitors have similar binding affinity with both GDP-bound and GTP-bound KRAS(G12D), and our crystallographic studies reveal the structural basis of inhibitor binding-induced switch-II pocket in KRAS(G12D), experimentally confirming the formation of a salt bridge between the piperazine moiety of the inhibitors and the Asp12 residue of the mutant protein. Guanosine Triphosphate 97-100 KRAS proto-oncogene, GTPase Homo sapiens 229-233 35053550-2 2022 In past decades, KRAS enjoyed the notorious reputation of being untargetable-that is, until the advent of G12C inhibitors, which put an end to this legend by covalently targeting the G12C (glycine to cysteine) substitution in the switch-II pocket of the protein, inhibiting the affinity of the mutant KRAS with GTP and subsequently the downstream signaling pathways, such as Raf/MEK/ERK. Guanosine Triphosphate 311-314 KRAS proto-oncogene, GTPase Homo sapiens 17-21 35425180-0 2022 Q61 mutant-mediated dynamics changes of the GTP-KRAS complex probed by Gaussian accelerated molecular dynamics and free energy landscapes. Guanosine Triphosphate 44-47 KRAS proto-oncogene, GTPase Homo sapiens 48-52 35425180-1 2022 Understanding the molecular mechanism of the GTP-KRAS binding is significant for improving the target roles of KRAS in cancer treatment. Guanosine Triphosphate 45-48 KRAS proto-oncogene, GTPase Homo sapiens 49-53 35425180-1 2022 Understanding the molecular mechanism of the GTP-KRAS binding is significant for improving the target roles of KRAS in cancer treatment. Guanosine Triphosphate 45-48 KRAS proto-oncogene, GTPase Homo sapiens 111-115 33723061-7 2021 In addition, we find that KRasG13D-GTP can allosterically increase the nucleotide exchange rate of KRas at the active site more than twofold compared to KRas-GTP. Guanosine Triphosphate 34-38 KRAS proto-oncogene, GTPase Homo sapiens 26-30 33309163-4 2021 Treatment of 26a with NCI-H358 cells resulted in down-regulation of KRAS-GTP levels and reduction of phosphorylation of downstream ERK and AKT dose-dependently. Guanosine Triphosphate 73-76 KRAS proto-oncogene, GTPase Homo sapiens 68-72 33739090-0 2021 Mutation-Induced Impacts on the Switch Transformations of the GDP- and GTP-Bound K-Ras: Insights from Multiple Replica Gaussian Accelerated Molecular Dynamics and Free Energy Analysis. Guanosine Triphosphate 71-74 KRAS proto-oncogene, GTPase Homo sapiens 81-86 33739090-2 2021 To unveil a molecular mechanism with regard to mutation-mediated tuning on the activity of K-Ras, multiple replica Gaussian accelerated molecular dynamics (MR-GaMD) simulations followed by analysis of free energy landscapes (FELs) are performed on the GDP- and GTP-bound wild-type (WT), G12V, and D33E K-Ras. Guanosine Triphosphate 261-264 KRAS proto-oncogene, GTPase Homo sapiens 91-96 33739090-4 2021 The information stemming from the analyses of FELs reveals that the conformations of SW1 and SW2 are in high disorders in the GDP- and GTP-associated WT and mutated K-Ras, possibly producing significant effect on binding of guanine nucleotide exchange factors or effectors to K-Ras. Guanosine Triphosphate 135-138 KRAS proto-oncogene, GTPase Homo sapiens 165-170 33739090-4 2021 The information stemming from the analyses of FELs reveals that the conformations of SW1 and SW2 are in high disorders in the GDP- and GTP-associated WT and mutated K-Ras, possibly producing significant effect on binding of guanine nucleotide exchange factors or effectors to K-Ras. Guanosine Triphosphate 135-138 KRAS proto-oncogene, GTPase Homo sapiens 276-281 33739090-5 2021 The interaction networks of GDP and GTP with K-Ras are identified and the results uncover that the instability in hydrogen-bonding interactions of SW1 with GDP and GTP is mostly responsible for conformational disorder of SW1 and SW2 as well as tunes the activity of oncogenic K-Ras. Guanosine Triphosphate 36-39 KRAS proto-oncogene, GTPase Homo sapiens 45-50 33739090-5 2021 The interaction networks of GDP and GTP with K-Ras are identified and the results uncover that the instability in hydrogen-bonding interactions of SW1 with GDP and GTP is mostly responsible for conformational disorder of SW1 and SW2 as well as tunes the activity of oncogenic K-Ras. Guanosine Triphosphate 36-39 KRAS proto-oncogene, GTPase Homo sapiens 276-281 33739090-5 2021 The interaction networks of GDP and GTP with K-Ras are identified and the results uncover that the instability in hydrogen-bonding interactions of SW1 with GDP and GTP is mostly responsible for conformational disorder of SW1 and SW2 as well as tunes the activity of oncogenic K-Ras. Guanosine Triphosphate 164-167 KRAS proto-oncogene, GTPase Homo sapiens 45-50 33739090-5 2021 The interaction networks of GDP and GTP with K-Ras are identified and the results uncover that the instability in hydrogen-bonding interactions of SW1 with GDP and GTP is mostly responsible for conformational disorder of SW1 and SW2 as well as tunes the activity of oncogenic K-Ras. Guanosine Triphosphate 164-167 KRAS proto-oncogene, GTPase Homo sapiens 276-281 33680360-6 2021 To address this, we performed molecular dynamics simulations (~30 mus in total) on unphosphorylated and phosphorylated K-Ras4B in GTP- and GDP-bound states, and on their complexes with GTPase cycle regulators (GAP and SOS) and the effector protein Raf. Guanosine Triphosphate 130-133 KRAS proto-oncogene, GTPase Homo sapiens 119-126 33680360-7 2021 We found that K-Ras4B dual phosphorylation mainly alters the conformation at the nucleotide binding site and creates disorder at the catalytic site, resulting in the enlargement of GDP binding pocket and the retard of Ras-GTP intrinsic hydrolysis. Guanosine Triphosphate 222-225 KRAS proto-oncogene, GTPase Homo sapiens 14-21 33723061-7 2021 In addition, we find that KRasG13D-GTP can allosterically increase the nucleotide exchange rate of KRas at the active site more than twofold compared to KRas-GTP. Guanosine Triphosphate 34-38 KRAS proto-oncogene, GTPase Homo sapiens 99-103 33723061-7 2021 In addition, we find that KRasG13D-GTP can allosterically increase the nucleotide exchange rate of KRas at the active site more than twofold compared to KRas-GTP. Guanosine Triphosphate 35-38 KRAS proto-oncogene, GTPase Homo sapiens 26-30 33723061-7 2021 In addition, we find that KRasG13D-GTP can allosterically increase the nucleotide exchange rate of KRas at the active site more than twofold compared to KRas-GTP. Guanosine Triphosphate 35-38 KRAS proto-oncogene, GTPase Homo sapiens 99-103 33145412-0 2020 GTP-State-Selective Cyclic Peptide Ligands of K-Ras(G12D) Block Its Interaction with Raf. Guanosine Triphosphate 0-3 KRAS proto-oncogene, GTPase Homo sapiens 46-51 32715349-4 2020 Despite its key importance in human disease, KRAS was assumed to be non-druggable for a long time since the protein seemingly lacks potential drug-binding pockets except the nucleotide-binding site, which is difficult to be targeted due to the high affinity of KRAS for both GDP and GTP. Guanosine Triphosphate 283-286 KRAS proto-oncogene, GTPase Homo sapiens 45-49 32715349-4 2020 Despite its key importance in human disease, KRAS was assumed to be non-druggable for a long time since the protein seemingly lacks potential drug-binding pockets except the nucleotide-binding site, which is difficult to be targeted due to the high affinity of KRAS for both GDP and GTP. Guanosine Triphosphate 283-286 KRAS proto-oncogene, GTPase Homo sapiens 261-265 33266473-0 2020 Influence of Cholesterol on the Orientation of the Farnesylated GTP-Bound KRas-4B Binding with Anionic Model Membranes. Guanosine Triphosphate 64-67 KRAS proto-oncogene, GTPase Homo sapiens 74-81 33153459-4 2020 One study proposes a mechanism that focuses on the inhibition of active, GTP-bound wild-type RAS, which is proposed to occur to a greater extent in KRAS G13D tumors due to the inability of KRAS G13D to bind NF1 well. Guanosine Triphosphate 73-76 KRAS proto-oncogene, GTPase Homo sapiens 148-152 33153459-4 2020 One study proposes a mechanism that focuses on the inhibition of active, GTP-bound wild-type RAS, which is proposed to occur to a greater extent in KRAS G13D tumors due to the inability of KRAS G13D to bind NF1 well. Guanosine Triphosphate 73-76 KRAS proto-oncogene, GTPase Homo sapiens 189-193 33153459-5 2020 The other study suggests NF1 can convert GTP-bound KRAS G13D to inactive, GDP-bound KRAS G13D. Guanosine Triphosphate 41-44 KRAS proto-oncogene, GTPase Homo sapiens 51-55 33153459-5 2020 The other study suggests NF1 can convert GTP-bound KRAS G13D to inactive, GDP-bound KRAS G13D. Guanosine Triphosphate 41-44 KRAS proto-oncogene, GTPase Homo sapiens 84-88 33145412-2 2020 These cyclic peptides show preferential binding to the GTP-bound state of K-Ras(G12D) over the GDP-bound state and block Ras-Raf interaction. Guanosine Triphosphate 55-58 KRAS proto-oncogene, GTPase Homo sapiens 74-79 33145412-5 2020 The union of G12D over wildtype selectivity and GTP state/GDP state selectivity is particularly desirable, considering that oncogenic K-Ras(G12D) exists predominantly in the GTP state in cancer cells, and wildtype K-Ras signaling is important for the maintenance of healthy cells. Guanosine Triphosphate 48-51 KRAS proto-oncogene, GTPase Homo sapiens 134-139 33145412-5 2020 The union of G12D over wildtype selectivity and GTP state/GDP state selectivity is particularly desirable, considering that oncogenic K-Ras(G12D) exists predominantly in the GTP state in cancer cells, and wildtype K-Ras signaling is important for the maintenance of healthy cells. Guanosine Triphosphate 174-177 KRAS proto-oncogene, GTPase Homo sapiens 134-139 33196710-2 2020 Although the different mutations of the KRAS gene have been identified decades ago, the development of drugs targeting the KRAS protein directly have not been successful due to the lack of small molecule binding sites and the extremely high affinity to cellular GTP. Guanosine Triphosphate 262-265 KRAS proto-oncogene, GTPase Homo sapiens 40-44 33196710-2 2020 Although the different mutations of the KRAS gene have been identified decades ago, the development of drugs targeting the KRAS protein directly have not been successful due to the lack of small molecule binding sites and the extremely high affinity to cellular GTP. Guanosine Triphosphate 262-265 KRAS proto-oncogene, GTPase Homo sapiens 123-127 32257057-5 2020 The complex contains two active GTP-bound KRas4B proteins forming a dimer through the allosteric lobe interface and two tandem RBD-CRD segments of Raf-1 interacting with the effector lobes at both ends of the KRas4B dimer. Guanosine Triphosphate 32-35 KRAS proto-oncogene, GTPase Homo sapiens 42-48 32636302-5 2020 Our previous data further showed that the E62K mutation impairs GAP activity for RAC2E62K As this disease mutation is also found in RAS GTPases, we assessed GAP-stimulated GTP hydrolysis for KRAS and observed a similar impairment, suggesting the mutation plays a conserved role in GAP activation. Guanosine Triphosphate 137-140 KRAS proto-oncogene, GTPase Homo sapiens 192-196 32227412-0 2020 Two Distinct Structures of Membrane-associated Homodimers of GTP- and GDP-bound KRAS4B Revealed by Paramagnetic Relaxation Enhancement. Guanosine Triphosphate 61-64 KRAS proto-oncogene, GTPase Homo sapiens 80-86 32227412-2 2020 We developed a system to study KRAS dimerization on nanodiscs using paramagnetic relaxation enhancement (PRE) NMR, and determined distinct structures of membrane-anchored KRAS dimers in the active GTP- and inactive GDP-loaded states. Guanosine Triphosphate 197-200 KRAS proto-oncogene, GTPase Homo sapiens 171-175 32486141-6 2020 We showed that the peptide acted as an inhibitor of mutant KRAS targets by [alpha-32P] guanosine triphosphate (GTP) binding assay. Guanosine Triphosphate 111-114 KRAS proto-oncogene, GTPase Homo sapiens 59-63 31219673-0 2019 Optical Control of GTP Affinity of K-Ras(G12C) by Photoswitchable Inhibitor. Guanosine Triphosphate 19-22 KRAS proto-oncogene, GTPase Homo sapiens 35-40 31219673-4 2019 Nucleotide exchange assay demonstrated the different efficacy to control GTP affinity by photoswitching of one potent compound PS-C2, which would be useful tool to probe the conformation of mutational K-Ras. Guanosine Triphosphate 73-76 KRAS proto-oncogene, GTPase Homo sapiens 201-206 31339036-12 2019 The orientation and dynamics of KRAS4b on the membrane are critical to understanding the mechanisms of oncoprotein signaling, and our results with the GDP-bound form show subtle differences from that published for GTP-KRAS4b. Guanosine Triphosphate 214-217 KRAS proto-oncogene, GTPase Homo sapiens 32-38 31827279-6 2019 Here we report a direct, GTP-dependent interaction between KRAS4A and hexokinase 1 (HK1) that alters the activity of the kinase, and thereby establish that HK1 is an effector of KRAS4A. Guanosine Triphosphate 25-28 KRAS proto-oncogene, GTPase Homo sapiens 59-65 31827279-6 2019 Here we report a direct, GTP-dependent interaction between KRAS4A and hexokinase 1 (HK1) that alters the activity of the kinase, and thereby establish that HK1 is an effector of KRAS4A. Guanosine Triphosphate 25-28 KRAS proto-oncogene, GTPase Homo sapiens 178-184 31611389-0 2019 KRAS G13D sensitivity to neurofibromin-mediated GTP hydrolysis. Guanosine Triphosphate 48-51 KRAS proto-oncogene, GTPase Homo sapiens 0-4 31611389-2 2019 KRAS mutations at codons 12, 13, or 61 are thought to prevent GAP protein-stimulated GTP hydrolysis and render KRAS-mutated colorectal cancers unresponsive to epidermal growth factor receptor (EGFR) inhibitors. Guanosine Triphosphate 85-88 KRAS proto-oncogene, GTPase Homo sapiens 0-4 31611389-4 2019 Neurofibromin protein (encoded by the NF1 gene) hydrolyzes GTP directly in complex with KRAS G13D, and KRAS G13D-mutated cells can respond to EGFR inhibitors in a neurofibromin-dependent manner. Guanosine Triphosphate 59-62 KRAS proto-oncogene, GTPase Homo sapiens 88-92 31611389-5 2019 Structures of the wild type and G13D mutant of KRAS in complex with neurofibromin (RasGAP domain) provide the structural basis for neurofibromin-mediated GTP hydrolysis. Guanosine Triphosphate 154-157 KRAS proto-oncogene, GTPase Homo sapiens 47-51 31339036-12 2019 The orientation and dynamics of KRAS4b on the membrane are critical to understanding the mechanisms of oncoprotein signaling, and our results with the GDP-bound form show subtle differences from that published for GTP-KRAS4b. Guanosine Triphosphate 214-217 KRAS proto-oncogene, GTPase Homo sapiens 218-224 31409810-3 2019 Here, we present local changes in K-Ras structure, conformation and dynamics upon G12D mutation, from long-timescale Molecular Dynamics simulations of active (GTP-bound) and inactive (GDP-bound) forms of wild-type and mutant K-Ras, with an integrated investigation of atomistic-level changes, local conformational shifts and correlated residue motions. Guanosine Triphosphate 159-162 KRAS proto-oncogene, GTPase Homo sapiens 34-39 31306575-7 2019 Intrinsic GTPase activity is directly monitored by the loss in mass of K-RAS bound to GTP, which corresponds to the release of phosphate. Guanosine Triphosphate 10-13 KRAS proto-oncogene, GTPase Homo sapiens 71-76 31853358-0 2019 Investigation of GTP-dependent dimerization of G12X K-Ras variants using ultraviolet photodissociation mass spectrometry. Guanosine Triphosphate 17-20 KRAS proto-oncogene, GTPase Homo sapiens 52-57 31853358-4 2019 Electrospray ionization (ESI) was used to transfer complexes of WT or G12X K-Ras bound to guanosine 5"-diphosphate (GDP) or GppNHp (non-hydrolyzable analogue of GTP) into the gas phase. Guanosine Triphosphate 161-164 KRAS proto-oncogene, GTPase Homo sapiens 75-80 31409810-4 2019 Our results reveal that the local changes in K-Ras are specific to bound nucleotide (GTP or GDP), and we provide a structural basis for this. Guanosine Triphosphate 85-88 KRAS proto-oncogene, GTPase Homo sapiens 45-50 29229665-2 2018 On the PM, the ubiquitously expressed Ras isoforms, H-, N-, and K-Ras, spatially segregate to nonoverlapping nanometer-sized domains, called nanoclusters, with further lateral segregation into nonoverlapping guanosine triphosphate (GTP)-bound and guanosine diphosphate (GDP)-bound nanoclusters. Guanosine Triphosphate 208-230 KRAS proto-oncogene, GTPase Homo sapiens 64-69 30930748-13 2019 Second, by advancing actin/myosin-based contraction through K-Ras.GTP/PI3K signaling, causing filopodia/lamellipodia to retract/internalize myelin-debris. Guanosine Triphosphate 66-69 KRAS proto-oncogene, GTPase Homo sapiens 60-65 30683722-6 2019 By preventing formation of the KRAS-SOS1 complex, these inhibitors block reloading of KRAS with GTP, leading to antiproliferative activity. Guanosine Triphosphate 96-99 KRAS proto-oncogene, GTPase Homo sapiens 31-35 30683722-6 2019 By preventing formation of the KRAS-SOS1 complex, these inhibitors block reloading of KRAS with GTP, leading to antiproliferative activity. Guanosine Triphosphate 96-99 KRAS proto-oncogene, GTPase Homo sapiens 86-90 29229665-2 2018 On the PM, the ubiquitously expressed Ras isoforms, H-, N-, and K-Ras, spatially segregate to nonoverlapping nanometer-sized domains, called nanoclusters, with further lateral segregation into nonoverlapping guanosine triphosphate (GTP)-bound and guanosine diphosphate (GDP)-bound nanoclusters. Guanosine Triphosphate 232-235 KRAS proto-oncogene, GTPase Homo sapiens 64-69 30097175-6 2018 Our simulations indicate that KRas4B-GTP interacts with the REM allosteric site more strongly than with the CDC25 catalytic site, consistent with its allosteric role in the GDP-to-GTP exchange. Guanosine Triphosphate 37-40 KRAS proto-oncogene, GTPase Homo sapiens 30-36 30097175-8 2018 The conformational change facilitates loading KRas4B-GDP at the catalytic site and opening the KRas4B nucleotide-binding site for GDP release and GTP binding. Guanosine Triphosphate 146-149 KRAS proto-oncogene, GTPase Homo sapiens 46-52 30097175-8 2018 The conformational change facilitates loading KRas4B-GDP at the catalytic site and opening the KRas4B nucleotide-binding site for GDP release and GTP binding. Guanosine Triphosphate 146-149 KRAS proto-oncogene, GTPase Homo sapiens 95-101 30097175-9 2018 GTP binding reduces the affinity of KRas4B-GTP to the CDC25 catalytic site, resulting in its release. Guanosine Triphosphate 0-3 KRAS proto-oncogene, GTPase Homo sapiens 36-42 29313669-2 2018 However, directly targeting oncogenic KRAS with small molecules in the nucleotide-binding site has been difficult because of the high affinity of KRAS for GDP and GTP. Guanosine Triphosphate 163-166 KRAS proto-oncogene, GTPase Homo sapiens 38-42 29808010-4 2018 KRAS-amplified gastric cancer models show marked overexpression of the KRAS protein and are insensitive to MAPK blockade owing to their capacity to adaptively respond by rapidly increasing KRAS-GTP levels. Guanosine Triphosphate 194-197 KRAS proto-oncogene, GTPase Homo sapiens 0-4 29808010-4 2018 KRAS-amplified gastric cancer models show marked overexpression of the KRAS protein and are insensitive to MAPK blockade owing to their capacity to adaptively respond by rapidly increasing KRAS-GTP levels. Guanosine Triphosphate 194-197 KRAS proto-oncogene, GTPase Homo sapiens 71-75 29808010-4 2018 KRAS-amplified gastric cancer models show marked overexpression of the KRAS protein and are insensitive to MAPK blockade owing to their capacity to adaptively respond by rapidly increasing KRAS-GTP levels. Guanosine Triphosphate 194-197 KRAS proto-oncogene, GTPase Homo sapiens 71-75 30104724-5 2018 Our findings illuminate a critical function for SHP2 in promoting oncogenic RAS/MAPK pathway activation in cancers with RAS-GTP-dependent oncogenic BRAF, NF1 loss and nucleotide-cycling oncogenic KRAS. Guanosine Triphosphate 124-127 KRAS proto-oncogene, GTPase Homo sapiens 196-200 29706533-1 2018 Structures of wild-type K-Ras from crystals obtained in the presence of guanosine triphosphate (GTP) or its analogs have remained elusive. Guanosine Triphosphate 72-94 KRAS proto-oncogene, GTPase Homo sapiens 24-29 29706533-1 2018 Structures of wild-type K-Ras from crystals obtained in the presence of guanosine triphosphate (GTP) or its analogs have remained elusive. Guanosine Triphosphate 96-99 KRAS proto-oncogene, GTPase Homo sapiens 24-29 29706533-3 2018 We present the crystal structure of wild-type K-Ras bound to the GTP analog GppCH2p, with K-Ras in the state 1 conformation. Guanosine Triphosphate 65-68 KRAS proto-oncogene, GTPase Homo sapiens 46-51 29706533-3 2018 We present the crystal structure of wild-type K-Ras bound to the GTP analog GppCH2p, with K-Ras in the state 1 conformation. Guanosine Triphosphate 65-68 KRAS proto-oncogene, GTPase Homo sapiens 90-95 29313669-2 2018 However, directly targeting oncogenic KRAS with small molecules in the nucleotide-binding site has been difficult because of the high affinity of KRAS for GDP and GTP. Guanosine Triphosphate 163-166 KRAS proto-oncogene, GTPase Homo sapiens 146-150 29313669-3 2018 We designed an engineered allele of KRAS and a covalent inhibitor that competes for GTP and GDP. Guanosine Triphosphate 84-87 KRAS proto-oncogene, GTPase Homo sapiens 36-40 29033317-2 2017 Here, we utilize disulfide tethering of a non-natural cysteine (K-Ras(M72C)) to identify a new switch-II pocket (S-IIP) binding ligand (2C07) that engages the active GTP state. Guanosine Triphosphate 166-169 KRAS proto-oncogene, GTPase Homo sapiens 64-69 27909058-6 2017 Although we initially hypothesized a role for active Ras protein signaling in exosome biogenesis, we found that GTP binding of K-Ras was dispensable for its packaging within extracellular nanovesicles and for the release of Alix. Guanosine Triphosphate 112-115 KRAS proto-oncogene, GTPase Homo sapiens 127-132 29199977-0 2017 Structural insight into the rearrangement of the switch I region in GTP-bound G12A K-Ras. Guanosine Triphosphate 68-71 KRAS proto-oncogene, GTPase Homo sapiens 83-88 29199977-1 2017 K-Ras, a molecular switch that regulates cell growth, apoptosis and metabolism, is activated when it undergoes a conformation change upon binding GTP and is deactivated following the hydrolysis of GTP to GDP. Guanosine Triphosphate 146-149 KRAS proto-oncogene, GTPase Homo sapiens 0-5 29199977-1 2017 K-Ras, a molecular switch that regulates cell growth, apoptosis and metabolism, is activated when it undergoes a conformation change upon binding GTP and is deactivated following the hydrolysis of GTP to GDP. Guanosine Triphosphate 197-200 KRAS proto-oncogene, GTPase Homo sapiens 0-5 29199977-2 2017 Hydrolysis of GTP in water is accelerated by coordination to K-Ras, where GTP adopts a high-energy conformation approaching the transition state. Guanosine Triphosphate 14-17 KRAS proto-oncogene, GTPase Homo sapiens 61-66 29199977-2 2017 Hydrolysis of GTP in water is accelerated by coordination to K-Ras, where GTP adopts a high-energy conformation approaching the transition state. Guanosine Triphosphate 74-77 KRAS proto-oncogene, GTPase Homo sapiens 61-66 29199977-3 2017 The G12A mutation reduces intrinsic K-Ras GTP hydrolysis by an unexplained mechanism. Guanosine Triphosphate 42-45 KRAS proto-oncogene, GTPase Homo sapiens 36-41 29199977-4 2017 Here, crystal structures of G12A K-Ras in complex with GDP, GTP, GTPgammaS and GppNHp, and of Q61A K-Ras in complex with GDP, are reported. Guanosine Triphosphate 60-63 KRAS proto-oncogene, GTPase Homo sapiens 33-38 29199977-5 2017 In the G12A K-Ras-GTP complex, the switch I region undergoes a significant reorganization such that the Tyr32 side chain points towards the GTP-binding pocket and forms a hydrogen bond to the GTP gamma-phosphate, effectively stabilizing GTP in its precatalytic state, increasing the activation energy required to reach the transition state and contributing to the reduced intrinsic GTPase activity of G12A K-Ras mutants. Guanosine Triphosphate 18-21 KRAS proto-oncogene, GTPase Homo sapiens 12-17 29199977-5 2017 In the G12A K-Ras-GTP complex, the switch I region undergoes a significant reorganization such that the Tyr32 side chain points towards the GTP-binding pocket and forms a hydrogen bond to the GTP gamma-phosphate, effectively stabilizing GTP in its precatalytic state, increasing the activation energy required to reach the transition state and contributing to the reduced intrinsic GTPase activity of G12A K-Ras mutants. Guanosine Triphosphate 18-21 KRAS proto-oncogene, GTPase Homo sapiens 406-411 29199977-5 2017 In the G12A K-Ras-GTP complex, the switch I region undergoes a significant reorganization such that the Tyr32 side chain points towards the GTP-binding pocket and forms a hydrogen bond to the GTP gamma-phosphate, effectively stabilizing GTP in its precatalytic state, increasing the activation energy required to reach the transition state and contributing to the reduced intrinsic GTPase activity of G12A K-Ras mutants. Guanosine Triphosphate 140-143 KRAS proto-oncogene, GTPase Homo sapiens 12-17 29199977-5 2017 In the G12A K-Ras-GTP complex, the switch I region undergoes a significant reorganization such that the Tyr32 side chain points towards the GTP-binding pocket and forms a hydrogen bond to the GTP gamma-phosphate, effectively stabilizing GTP in its precatalytic state, increasing the activation energy required to reach the transition state and contributing to the reduced intrinsic GTPase activity of G12A K-Ras mutants. Guanosine Triphosphate 140-143 KRAS proto-oncogene, GTPase Homo sapiens 12-17 28259298-2 2017 Mutations of K-RAS oncogene lead to an accumulation of GTP-bound proteins that maintains an active conformation. Guanosine Triphosphate 55-58 KRAS proto-oncogene, GTPase Homo sapiens 13-18 28597297-5 2017 We discuss (1) GTP-bound KRas4B activation through membrane attachment; (2) how farnesylation and palmitoylation can promote isoform functional specificity; (3) calmodulin binding and PI3K activation; (4) how Ras activates its RASSF5 cofactor, thereby stimulating signaling of the Hippo pathway and repressing proliferation; and (5) how intrinsically disordered segments in Raf help its attachment to the membrane and activation. Guanosine Triphosphate 15-18 KRAS proto-oncogene, GTPase Homo sapiens 25-31 28781124-3 2017 We demonstrate that covalent quinazoline-based switch II pocket (SIIP) compounds effectively suppress GTP loading of KRAS G12C, MAPK phosphorylation, and the growth of cancer cells harboring G12C. Guanosine Triphosphate 102-105 KRAS proto-oncogene, GTPase Homo sapiens 117-121 28153726-5 2017 KRpep-2 showed more than 10-fold binding- and inhibition-selectivity to K-Ras(G12D), both in SPR analysis and GDP/GTP exchange enzyme assay. Guanosine Triphosphate 114-117 KRAS proto-oncogene, GTPase Homo sapiens 72-77 27410739-6 2016 In this biophysical study, we investigated the effect of Ca(2+)/CaM on the interaction of GDP- and GTP-loaded K-Ras4B with heterogeneous model biomembranes by using a combination of different spectroscopic and imaging techniques. Guanosine Triphosphate 99-102 KRAS proto-oncogene, GTPase Homo sapiens 110-117 27845397-6 2016 Analyzing nucleotide-dependent intrinsic K-Ras motions with the new approach yields predictions that agree with the literature, showing that GTP-binding stabilizes K-Ras motions and leads to residue correlations with relatively long characteristic decay times. Guanosine Triphosphate 141-144 KRAS proto-oncogene, GTPase Homo sapiens 41-46 27845397-6 2016 Analyzing nucleotide-dependent intrinsic K-Ras motions with the new approach yields predictions that agree with the literature, showing that GTP-binding stabilizes K-Ras motions and leads to residue correlations with relatively long characteristic decay times. Guanosine Triphosphate 141-144 KRAS proto-oncogene, GTPase Homo sapiens 164-169 27665622-3 2016 Complexes between K-Ras or the G12X mutants and guanosine 5"-diphosphate (GDP) or GDPnP (a stable GTP analogue) were transferred to the gas phase by nano-electrospray ionization and characterized using UVPD. Guanosine Triphosphate 98-101 KRAS proto-oncogene, GTPase Homo sapiens 18-23 26873344-6 2016 EXPERT OPINION: An oncogenic GTP-bound K-Ras4B/CaM/PI3Kalpha complex is supported by available experimental and clinical data; therefore, targeting it may address a pressing therapeutic need. Guanosine Triphosphate 29-32 KRAS proto-oncogene, GTPase Homo sapiens 39-46 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 KRAS proto-oncogene, GTPase Homo sapiens 105-112 26977877-2 2016 The new findings argue that the perception that mutant KRAS is persistently frozen in its active GTP-bound form may not be accurate. Guanosine Triphosphate 97-100 KRAS proto-oncogene, GTPase Homo sapiens 55-59 26522388-7 2015 Farnesylated and methylated KRAS4b is fully active in hydrolyzing GTP, binds RAF-RBD on lipid Nanodiscs and interacts with the known farnesyl-binding protein PDEdelta. Guanosine Triphosphate 66-69 KRAS proto-oncogene, GTPase Homo sapiens 28-34 26854235-4 2016 The AGO2 N-terminal domain directly binds the Switch II region of KRAS, agnostic of nucleotide (GDP/GTP) binding. Guanosine Triphosphate 100-103 KRAS proto-oncogene, GTPase Homo sapiens 66-70 26854029-4 2016 Recombinant K-Ras(G60_A66dup) and K-Ras(E62_A66dup) proteins display reduced intrinsic GTP hydrolysis rates, accumulate in the GTP-bound conformation and are resistant to GAP-mediated GTP hydrolysis. Guanosine Triphosphate 87-90 KRAS proto-oncogene, GTPase Homo sapiens 12-17 26854029-4 2016 Recombinant K-Ras(G60_A66dup) and K-Ras(E62_A66dup) proteins display reduced intrinsic GTP hydrolysis rates, accumulate in the GTP-bound conformation and are resistant to GAP-mediated GTP hydrolysis. Guanosine Triphosphate 87-90 KRAS proto-oncogene, GTPase Homo sapiens 34-39 26854029-4 2016 Recombinant K-Ras(G60_A66dup) and K-Ras(E62_A66dup) proteins display reduced intrinsic GTP hydrolysis rates, accumulate in the GTP-bound conformation and are resistant to GAP-mediated GTP hydrolysis. Guanosine Triphosphate 127-130 KRAS proto-oncogene, GTPase Homo sapiens 12-17 26854029-4 2016 Recombinant K-Ras(G60_A66dup) and K-Ras(E62_A66dup) proteins display reduced intrinsic GTP hydrolysis rates, accumulate in the GTP-bound conformation and are resistant to GAP-mediated GTP hydrolysis. Guanosine Triphosphate 127-130 KRAS proto-oncogene, GTPase Homo sapiens 34-39 26854029-4 2016 Recombinant K-Ras(G60_A66dup) and K-Ras(E62_A66dup) proteins display reduced intrinsic GTP hydrolysis rates, accumulate in the GTP-bound conformation and are resistant to GAP-mediated GTP hydrolysis. Guanosine Triphosphate 127-130 KRAS proto-oncogene, GTPase Homo sapiens 12-17 26854029-4 2016 Recombinant K-Ras(G60_A66dup) and K-Ras(E62_A66dup) proteins display reduced intrinsic GTP hydrolysis rates, accumulate in the GTP-bound conformation and are resistant to GAP-mediated GTP hydrolysis. Guanosine Triphosphate 127-130 KRAS proto-oncogene, GTPase Homo sapiens 34-39 26453300-0 2015 GTP Binding and Oncogenic Mutations May Attenuate Hypervariable Region (HVR)-Catalytic Domain Interactions in Small GTPase K-Ras4B, Exposing the Effector Binding Site. Guanosine Triphosphate 0-3 KRAS proto-oncogene, GTPase Homo sapiens 123-130 26453300-4 2015 Here, using molecular dynamics simulations and NMR, we aim to figure out the effects of nucleotides (GTP and GDP) and frequent (G12C, G12D, G12V, G13D, and Q61H) and infrequent (E37K and R164Q) oncogenic mutations on full-length K-Ras4B. Guanosine Triphosphate 101-104 KRAS proto-oncogene, GTPase Homo sapiens 229-236 26453300-7 2015 The looser association in K-Ras4B(WT)-GTP may release the HVR. Guanosine Triphosphate 36-41 KRAS proto-oncogene, GTPase Homo sapiens 26-33 26453300-8 2015 Some of the oncogenic mutations weaken the HVR-catalytic domain association in the K-Ras4B-GDP/-GTP bound states, which may facilitate the HVR disassociation in a nucleotide-independent manner, thereby up-regulating oncogenic Ras signaling. Guanosine Triphosphate 96-99 KRAS proto-oncogene, GTPase Homo sapiens 83-90 26960760-2 2016 In cancers driven by mutant K-Ras, the protein is locked in the active, GTP-bound state constitutively, through a defect in the off-switch mechanism. Guanosine Triphosphate 72-75 KRAS proto-oncogene, GTPase Homo sapiens 28-33 26960760-4 2016 K-Ras is a member of a large family of related proteins, which share very similar GDP/GTP-binding domains, making specific therapies more difficult. Guanosine Triphosphate 86-89 KRAS proto-oncogene, GTPase Homo sapiens 0-5 26902995-3 2016 Even though all impair GAP-assisted GTP GDP hydrolysis, the mutation frequencies of K-Ras4B in human cancers vary. Guanosine Triphosphate 36-39 KRAS proto-oncogene, GTPase Homo sapiens 86-93 26902995-5 2016 In total, we performed 6.4 mus molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4B(WT)-GTP/GDP) catalytic domain, the K-Ras4B(WT)-GTP-GAP complex, and the mutants (K-Ras4B(G12C/G12D/G12V)-GTP/GDP, K-Ras4B(G13D)-GTP/GDP, K-Ras4B(Q61H)-GTP/GDP) and their complexes with GAP. Guanosine Triphosphate 100-103 KRAS proto-oncogene, GTPase Homo sapiens 88-95 26902995-5 2016 In total, we performed 6.4 mus molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4B(WT)-GTP/GDP) catalytic domain, the K-Ras4B(WT)-GTP-GAP complex, and the mutants (K-Ras4B(G12C/G12D/G12V)-GTP/GDP, K-Ras4B(G13D)-GTP/GDP, K-Ras4B(Q61H)-GTP/GDP) and their complexes with GAP. Guanosine Triphosphate 100-103 KRAS proto-oncogene, GTPase Homo sapiens 88-95 26902995-5 2016 In total, we performed 6.4 mus molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4B(WT)-GTP/GDP) catalytic domain, the K-Ras4B(WT)-GTP-GAP complex, and the mutants (K-Ras4B(G12C/G12D/G12V)-GTP/GDP, K-Ras4B(G13D)-GTP/GDP, K-Ras4B(Q61H)-GTP/GDP) and their complexes with GAP. Guanosine Triphosphate 100-103 KRAS proto-oncogene, GTPase Homo sapiens 88-95 26902995-5 2016 In total, we performed 6.4 mus molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4B(WT)-GTP/GDP) catalytic domain, the K-Ras4B(WT)-GTP-GAP complex, and the mutants (K-Ras4B(G12C/G12D/G12V)-GTP/GDP, K-Ras4B(G13D)-GTP/GDP, K-Ras4B(Q61H)-GTP/GDP) and their complexes with GAP. Guanosine Triphosphate 100-103 KRAS proto-oncogene, GTPase Homo sapiens 88-95 26902995-7 2016 These comprehensive simulations reveal that in solution K-Ras4B(WT)-GTP exists in two, active and inactive, conformations. Guanosine Triphosphate 66-71 KRAS proto-oncogene, GTPase Homo sapiens 56-63 26902995-8 2016 Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4B(G12C/G12D)-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. Guanosine Triphosphate 101-104 KRAS proto-oncogene, GTPase Homo sapiens 93-100 26902995-8 2016 Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4B(G12C/G12D)-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. Guanosine Triphosphate 101-104 KRAS proto-oncogene, GTPase Homo sapiens 109-116 26595770-5 2016 Loss of SNORD50A and SNORD50B increased the amount of GTP-bound, active K-Ras and hyperactivated Ras-ERK1/ERK2 signaling. Guanosine Triphosphate 54-57 KRAS proto-oncogene, GTPase Homo sapiens 72-77 26085527-5 2015 Calmodulin selectively binds to GTP-bound K-Ras4B; but not to other Ras isoforms. Guanosine Triphosphate 32-35 KRAS proto-oncogene, GTPase Homo sapiens 42-49 26080442-6 2015 We found that at endogenous expression levels KRas forms dimers, and KRas(G12D), a mutant that constitutively binds GTP, activates MAPK. Guanosine Triphosphate 116-119 KRAS proto-oncogene, GTPase Homo sapiens 69-73 26051715-0 2015 GTP-Dependent K-Ras Dimerization. Guanosine Triphosphate 0-3 KRAS proto-oncogene, GTPase Homo sapiens 14-19 26051715-4 2015 Here, we show that the GTP-bound catalytic domain of K-Ras4B, a highly oncogenic splice variant of the K-Ras isoform, forms stable homodimers. Guanosine Triphosphate 23-26 KRAS proto-oncogene, GTPase Homo sapiens 53-60 26051715-4 2015 Here, we show that the GTP-bound catalytic domain of K-Ras4B, a highly oncogenic splice variant of the K-Ras isoform, forms stable homodimers. Guanosine Triphosphate 23-26 KRAS proto-oncogene, GTPase Homo sapiens 53-58 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 KRAS proto-oncogene, GTPase Homo sapiens 59-63 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 KRAS proto-oncogene, GTPase Homo sapiens 106-110 25902334-6 2015 We now report that this mutation reduced the level of GTP-bound KRAS and impaired RAS signaling stimulated by the growth factor EGF. Guanosine Triphosphate 54-57 KRAS proto-oncogene, GTPase Homo sapiens 64-68 24300897-1 2013 Oncogenic K-Ras proteins, such as K-Ras(G12D), accumulate in the active, guanosine triphosphate (GTP)-bound conformation and stimulate signaling through effector kinases. Guanosine Triphosphate 73-95 KRAS proto-oncogene, GTPase Homo sapiens 10-15 24402942-1 2014 SUMMARY: Mutations that activate the small GTP-binding protein KRAS are the most common oncogenic event in human tumors. Guanosine Triphosphate 43-46 KRAS proto-oncogene, GTPase Homo sapiens 63-67 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 KRAS proto-oncogene, GTPase Homo sapiens 90-95 25695162-1 2015 Constitutively active mutant KRas displays a reduced rate of GTP hydrolysis via both intrinsic and GTPase-activating protein-catalyzed mechanisms, resulting in the perpetual activation of Ras pathways. Guanosine Triphosphate 61-64 KRAS proto-oncogene, GTPase Homo sapiens 29-33 24338482-4 2014 Furthermore, the dynamics and function of negative regulation of GTP-loaded K-Ras have not been fully investigated. Guanosine Triphosphate 65-68 KRAS proto-oncogene, GTPase Homo sapiens 76-81 24338482-11 2014 Our results indicate the existence of GTP-loaded K-Ras orthologue-specific degradation system in Dictyostelium, and further identification of the responsible E3-ligase may provide a novel therapeutic approach against K-Ras-mutated cancers. Guanosine Triphosphate 38-41 KRAS proto-oncogene, GTPase Homo sapiens 49-54 24338482-11 2014 Our results indicate the existence of GTP-loaded K-Ras orthologue-specific degradation system in Dictyostelium, and further identification of the responsible E3-ligase may provide a novel therapeutic approach against K-Ras-mutated cancers. Guanosine Triphosphate 38-41 KRAS proto-oncogene, GTPase Homo sapiens 217-222 24470016-12 2014 The produced post-translationally modified K-Ras 4B is active in a number of assays, including a GTP hydrolysis assay, Raf-1 binding assay, and surface plasmon resonance-based phospholipid binding assay. Guanosine Triphosphate 97-100 KRAS proto-oncogene, GTPase Homo sapiens 43-51 24247240-6 2013 This mechanism of Ras activation is distinct from K-Ras monoubiquitination at Lys-147, which leads to impaired regulator-mediated GTP hydrolysis. Guanosine Triphosphate 130-133 KRAS proto-oncogene, GTPase Homo sapiens 50-55 24297914-4 2013 Here we have explored the mechanism of phospho-K-Ras4B toxicity and found that GTP-bound, phosphorylated K-Ras4B associates with inositol trisphosphate receptors on the ER in a Bcl-xL-dependent fashion and, in so doing, blocks the ability of Bcl-xL to potentiate the InsP3 regulated flux of calcium from ER to mitochondria that is required for efficient respiration, inhibition of autophagy, and cell survival. Guanosine Triphosphate 79-82 KRAS proto-oncogene, GTPase Homo sapiens 47-54 24297914-4 2013 Here we have explored the mechanism of phospho-K-Ras4B toxicity and found that GTP-bound, phosphorylated K-Ras4B associates with inositol trisphosphate receptors on the ER in a Bcl-xL-dependent fashion and, in so doing, blocks the ability of Bcl-xL to potentiate the InsP3 regulated flux of calcium from ER to mitochondria that is required for efficient respiration, inhibition of autophagy, and cell survival. Guanosine Triphosphate 79-82 KRAS proto-oncogene, GTPase Homo sapiens 105-112 24256730-0 2013 K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Guanosine Triphosphate 46-49 KRAS proto-oncogene, GTPase Homo sapiens 0-5 24256730-9 2013 Binding of these inhibitors to K-Ras(G12C) disrupts both switch-I and switch-II, subverting the native nucleotide preference to favour GDP over GTP and impairing binding to Raf. Guanosine Triphosphate 144-147 KRAS proto-oncogene, GTPase Homo sapiens 31-36 23943869-2 2013 Although these mutations induce the generation of a constitutively GTP-loaded, active form of K-Ras, phosphorylation at Ser181 within the C-terminal hypervariable region can modulate oncogenic K-Ras function without affecting the in vitro affinity for its effector Raf-1. Guanosine Triphosphate 67-70 KRAS proto-oncogene, GTPase Homo sapiens 94-99 24300897-1 2013 Oncogenic K-Ras proteins, such as K-Ras(G12D), accumulate in the active, guanosine triphosphate (GTP)-bound conformation and stimulate signaling through effector kinases. Guanosine Triphosphate 73-95 KRAS proto-oncogene, GTPase Homo sapiens 34-39 24300897-1 2013 Oncogenic K-Ras proteins, such as K-Ras(G12D), accumulate in the active, guanosine triphosphate (GTP)-bound conformation and stimulate signaling through effector kinases. Guanosine Triphosphate 97-100 KRAS proto-oncogene, GTPase Homo sapiens 10-15 24300897-1 2013 Oncogenic K-Ras proteins, such as K-Ras(G12D), accumulate in the active, guanosine triphosphate (GTP)-bound conformation and stimulate signaling through effector kinases. Guanosine Triphosphate 97-100 KRAS proto-oncogene, GTPase Homo sapiens 34-39 23737504-5 2013 As expected for inhibitors of exchange factor binding, AGP derivatives reduced GTP loading of wild-type K-Ras in response to acute EGF stimulation with a concomitant reduction in MAPK activation. Guanosine Triphosphate 79-82 KRAS proto-oncogene, GTPase Homo sapiens 104-109 23437064-4 2013 The potential of mean force (PMF) simulations were carried out to determine the free energy profiles of the binding processes of GTP interacting with wild-type (WT) KRAS and its mutants (MT). Guanosine Triphosphate 129-132 KRAS proto-oncogene, GTPase Homo sapiens 165-169 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 KRAS proto-oncogene, GTPase Homo sapiens 45-49 22721555-4 2012 In this study, the effect of PDEdelta on the interaction of GDP- and GTP-loaded K-Ras4B with neutral and anionic model biomembranes has been investigated by a combination of different spectroscopic and imaging techniques. Guanosine Triphosphate 69-72 KRAS proto-oncogene, GTPase Homo sapiens 80-87 23027861-3 2012 On one hand, the activated K-Ras up-regulates the expression of DNA methyltransferases and enhances the binding of DNA methyltransferase 1 to the MEN1 promoter, leading to increased DNA methylation at the MEN1 gene in lung cancer cells; on the other hand, menin reduces the level of active Ras-GTP at least partly by preventing GRB2 and SOS1 from binding to Ras, without affecting the expression of GRB2 and SOS1. Guanosine Triphosphate 294-297 KRAS proto-oncogene, GTPase Homo sapiens 27-32 22302539-6 2012 NS-associated KRAS mutation resulted in Erk activation and active Ras-GTP levels, and exhibited mild cell proliferation. Guanosine Triphosphate 70-73 KRAS proto-oncogene, GTPase Homo sapiens 14-18 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 KRAS proto-oncogene, GTPase Homo sapiens 18-23 22252770-2 2011 These mutations determine single aminoacidic substitutions in the GTPase pocket leading to a block of the GTP hydrolytic activity of the K-ras p21 protein, and therefore to its constitutive activation. Guanosine Triphosphate 66-69 KRAS proto-oncogene, GTPase Homo sapiens 137-142 22205714-5 2012 Importantly, resistance also correlated with increased levels of RAS-GTP, and sequencing of RAS genes revealed a rare activating mutation in KRAS, resulting in a K117N change in the KRAS protein. Guanosine Triphosphate 69-72 KRAS proto-oncogene, GTPase Homo sapiens 141-145 22205714-5 2012 Importantly, resistance also correlated with increased levels of RAS-GTP, and sequencing of RAS genes revealed a rare activating mutation in KRAS, resulting in a K117N change in the KRAS protein. Guanosine Triphosphate 69-72 KRAS proto-oncogene, GTPase Homo sapiens 182-186 22359497-5 2012 Moreover, a d/xi plot classifies the available Ras x-ray structures and MD-derived K-ras conformers into active GTP-, intermediate GTP-, inactive GDP-bound, and nucleotide-free conformational states. Guanosine Triphosphate 112-115 KRAS proto-oncogene, GTPase Homo sapiens 83-88 22359497-5 2012 Moreover, a d/xi plot classifies the available Ras x-ray structures and MD-derived K-ras conformers into active GTP-, intermediate GTP-, inactive GDP-bound, and nucleotide-free conformational states. Guanosine Triphosphate 131-134 KRAS proto-oncogene, GTPase Homo sapiens 83-88 21386094-4 2011 Here, we report that monoubiquitination of lysine-147 in the guanine nucleotide-binding motif of wild-type K-Ras could lead to enhanced GTP loading. Guanosine Triphosphate 136-139 KRAS proto-oncogene, GTPase Homo sapiens 107-112 21386094-6 2011 Thus, monoubiquitination could enhance GTP loading on K-Ras and increase its affinity for specific downstream effectors, providing a previously unidentified mechanism for Ras activation. Guanosine Triphosphate 39-42 KRAS proto-oncogene, GTPase Homo sapiens 54-59 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 KRAS proto-oncogene, GTPase Homo sapiens 37-41 22102901-1 2011 BACKGROUND: Galectin-3 (Gal-3) and active (GTP-bound) K-Ras contribute to the malignant phenotype of many human tumors by increasing the rate of cell proliferation, survival, and migration. Guanosine Triphosphate 43-46 KRAS proto-oncogene, GTPase Homo sapiens 54-59 22102901-2 2011 These Gal-3-mediated effects result from a selective binding to K-Ras.GTP, causing increased nanoclustering in the cell membrane and leading to robust Ras signaling. Guanosine Triphosphate 70-73 KRAS proto-oncogene, GTPase Homo sapiens 64-69 22102901-5 2011 We found that knockout of Gal-3 induced strong downregulation (~60%) of K-Ras and K-Ras.GTP. Guanosine Triphosphate 88-91 KRAS proto-oncogene, GTPase Homo sapiens 82-87 22102901-7 2011 These additional effects are probably attributable to inhibition of the weak interactions of K-Ras.GTP with Gal-1. Guanosine Triphosphate 99-102 KRAS proto-oncogene, GTPase Homo sapiens 93-98 20643072-2 2010 Following growth factor receptor activation K-Ras.GTP forms nanoclusters on the plasma membrane through interaction with the scaffold protein galectin-3. Guanosine Triphosphate 50-53 KRAS proto-oncogene, GTPase Homo sapiens 44-49 20846262-3 2010 The KRAS gene, belonging to the RAS gene family, encodes a membrane-bound 21-kd guanosine triphosphate (GTP)-binding protein. Guanosine Triphosphate 80-102 KRAS proto-oncogene, GTPase Homo sapiens 4-8 20846262-3 2010 The KRAS gene, belonging to the RAS gene family, encodes a membrane-bound 21-kd guanosine triphosphate (GTP)-binding protein. Guanosine Triphosphate 104-107 KRAS proto-oncogene, GTPase Homo sapiens 4-8 20643072-4 2010 To explore the mechanisms underlying K-Ras.GTP nanocluster formation, we developed a mathematical model of K-Ras-galectin-3 interactions. Guanosine Triphosphate 43-46 KRAS proto-oncogene, GTPase Homo sapiens 37-42 20643072-4 2010 To explore the mechanisms underlying K-Ras.GTP nanocluster formation, we developed a mathematical model of K-Ras-galectin-3 interactions. Guanosine Triphosphate 43-46 KRAS proto-oncogene, GTPase Homo sapiens 107-112 20643072-7 2010 The resulting model accurately replicates critical features of K-Ras nanoclustering, including a fixed ratio of clustered K-Ras.GTP to monomeric K-Ras.GTP that is independent of the concentration of K-Ras.GTP. Guanosine Triphosphate 128-131 KRAS proto-oncogene, GTPase Homo sapiens 63-68 20643072-7 2010 The resulting model accurately replicates critical features of K-Ras nanoclustering, including a fixed ratio of clustered K-Ras.GTP to monomeric K-Ras.GTP that is independent of the concentration of K-Ras.GTP. Guanosine Triphosphate 128-131 KRAS proto-oncogene, GTPase Homo sapiens 122-127 20643072-7 2010 The resulting model accurately replicates critical features of K-Ras nanoclustering, including a fixed ratio of clustered K-Ras.GTP to monomeric K-Ras.GTP that is independent of the concentration of K-Ras.GTP. Guanosine Triphosphate 128-131 KRAS proto-oncogene, GTPase Homo sapiens 122-127 20643072-7 2010 The resulting model accurately replicates critical features of K-Ras nanoclustering, including a fixed ratio of clustered K-Ras.GTP to monomeric K-Ras.GTP that is independent of the concentration of K-Ras.GTP. Guanosine Triphosphate 128-131 KRAS proto-oncogene, GTPase Homo sapiens 122-127 20643072-7 2010 The resulting model accurately replicates critical features of K-Ras nanoclustering, including a fixed ratio of clustered K-Ras.GTP to monomeric K-Ras.GTP that is independent of the concentration of K-Ras.GTP. Guanosine Triphosphate 151-154 KRAS proto-oncogene, GTPase Homo sapiens 63-68 20643072-7 2010 The resulting model accurately replicates critical features of K-Ras nanoclustering, including a fixed ratio of clustered K-Ras.GTP to monomeric K-Ras.GTP that is independent of the concentration of K-Ras.GTP. Guanosine Triphosphate 151-154 KRAS proto-oncogene, GTPase Homo sapiens 63-68 20643072-8 2010 The model reproduces experimental results showing that the cytosolic level of galectin-3 determines the magnitude of the K-Ras.GTP clustered fraction and illustrates that nanoclustering is regulated by key nonequilibrium processes. Guanosine Triphosphate 127-130 KRAS proto-oncogene, GTPase Homo sapiens 121-126 20570890-5 2010 Exon 4 KRAS mutations, all of which were identified at amino acid residues K117 and A146, were associated with lower levels of GTP-bound RAS in isogenic models. Guanosine Triphosphate 127-130 KRAS proto-oncogene, GTPase Homo sapiens 7-11 20532039-7 2010 Hypoxia consistently increased the levels of activated, GTP-bound K-ras in colon cancer cell lines with a wild-type KRAS gene, and this depended upon the activation of c-Src. Guanosine Triphosphate 56-59 KRAS proto-oncogene, GTPase Homo sapiens 66-71 20532039-7 2010 Hypoxia consistently increased the levels of activated, GTP-bound K-ras in colon cancer cell lines with a wild-type KRAS gene, and this depended upon the activation of c-Src. Guanosine Triphosphate 56-59 KRAS proto-oncogene, GTPase Homo sapiens 116-120 19583261-8 2009 The hypervariable region of K-Ras4B binds specifically to the C-terminal domain of Ca(2+)-loaded calmodulin with micromolar affinity, while the GTP-gamma-S-loaded catalytic domain of K-Ras4B may interact with the N-terminal domain of calmodulin. Guanosine Triphosphate 144-147 KRAS proto-oncogene, GTPase Homo sapiens 28-35 20585519-7 2010 The increase in clustered K-Ras-GTP enhances signaling through the MAPK pathway. Guanosine Triphosphate 32-35 KRAS proto-oncogene, GTPase Homo sapiens 26-31 18615637-6 2008 K-Ras-GTP levels and PI3K activity increased during normal phagocytosis and decreased during FTS-inhibited phagocytosis. Guanosine Triphosphate 6-9 KRAS proto-oncogene, GTPase Homo sapiens 0-5 19064407-6 2008 The K-Ras oncoprotein controls transduction of signals required for proliferation, differentiation, and survival, mainly acting as guanosine diphosphate/guanosine triphosphate-regulated binary switches located at the inner surface of the plasma membrane. Guanosine Triphosphate 153-175 KRAS proto-oncogene, GTPase Homo sapiens 4-9 19545448-12 2009 The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Guanosine Triphosphate 13-16 KRAS proto-oncogene, GTPase Homo sapiens 23-27 19545448-12 2009 The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Guanosine Triphosphate 13-16 KRAS proto-oncogene, GTPase Homo sapiens 103-107 19545448-12 2009 The level of GTP-bound KRAS was elevated following serum stimulation in cells with amplified wild-type KRAS, but not in cells with amplified mutant KRAS. Guanosine Triphosphate 13-16 KRAS proto-oncogene, GTPase Homo sapiens 103-107 21686750-6 2009 The F156L mutant K-Ras protein accumulated in the active, guanosine triphosphate-bound conformation and affected downstream signalling. Guanosine Triphosphate 58-80 KRAS proto-oncogene, GTPase Homo sapiens 17-22 18413234-3 2008 Binding of K-Ras to Gal-3 stabilizes K-Ras in its active (GTP-bound) state. Guanosine Triphosphate 58-61 KRAS proto-oncogene, GTPase Homo sapiens 11-16 18458061-2 2008 We show using high-resolution spatial mapping that Raf-1 is recruited to and retained in K-Ras-GTP nanoclusters. Guanosine Triphosphate 95-98 KRAS proto-oncogene, GTPase Homo sapiens 89-94 18458061-4 2008 Similarly, upon epidermal growth factor receptor activation, Raf-1 is preferentially recruited to K-Ras-GTP and not H-Ras-GTP nanoclusters. Guanosine Triphosphate 104-107 KRAS proto-oncogene, GTPase Homo sapiens 98-103 18413234-3 2008 Binding of K-Ras to Gal-3 stabilizes K-Ras in its active (GTP-bound) state. Guanosine Triphosphate 58-61 KRAS proto-oncogene, GTPase Homo sapiens 37-42 18413234-5 2008 First, comparative analysis of various cancer cell lines (glioblastomas, breast cancer cells and ovarian carcinomas) showed a positive correlation between low N-Ras-GTP/high K-Ras-GTP phenotype and Gal-3 expression levels. Guanosine Triphosphate 180-183 KRAS proto-oncogene, GTPase Homo sapiens 174-179 17974974-8 2007 Moreover, we show an increase in total Ras activity in Hs-RbAp48-hi cells with K-Ras-GTP becoming the dominant isoform. Guanosine Triphosphate 85-88 KRAS proto-oncogene, GTPase Homo sapiens 79-84 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 KRAS proto-oncogene, GTPase Homo sapiens 65-70 18701484-3 2008 We show here that K-Ras.GTP recruits Galectin-3 (Gal-3) from the cytosol to the plasma membrane where it becomes an integral nanocluster component. Guanosine Triphosphate 24-27 KRAS proto-oncogene, GTPase Homo sapiens 18-23 18701484-4 2008 Importantly, we show that the cytosolic level of Gal-3 determines the magnitude of K-Ras.GTP nanoclustering and signal output. Guanosine Triphosphate 89-92 KRAS proto-oncogene, GTPase Homo sapiens 83-88 18701484-7 2008 Gal-3(V125A) interaction with K-Ras.GTP reduces K-Ras.GTP nanocluster formation, which abrogates signal output from the Raf/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK; MEK) pathway. Guanosine Triphosphate 36-39 KRAS proto-oncogene, GTPase Homo sapiens 30-35 18701484-7 2008 Gal-3(V125A) interaction with K-Ras.GTP reduces K-Ras.GTP nanocluster formation, which abrogates signal output from the Raf/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK; MEK) pathway. Guanosine Triphosphate 36-39 KRAS proto-oncogene, GTPase Homo sapiens 48-53 18701484-7 2008 Gal-3(V125A) interaction with K-Ras.GTP reduces K-Ras.GTP nanocluster formation, which abrogates signal output from the Raf/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK; MEK) pathway. Guanosine Triphosphate 54-57 KRAS proto-oncogene, GTPase Homo sapiens 30-35 18701484-7 2008 Gal-3(V125A) interaction with K-Ras.GTP reduces K-Ras.GTP nanocluster formation, which abrogates signal output from the Raf/mitogen-activated protein (MAP)/extracellular signal-regulated kinase (ERK; MEK) pathway. Guanosine Triphosphate 54-57 KRAS proto-oncogene, GTPase Homo sapiens 48-53 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 KRAS proto-oncogene, GTPase Homo sapiens 14-18