PMID-sentid Pub_year Sent_text comp_official_name comp_offsetprotein_name organism prot_offset 15985432-2 2005 Previous data show that flow stimulates SHP2 translocation to cell membranes and binding to phosphotyrosine proteins. Phosphotyrosine 92-107 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 40-44 16129412-10 2005 The adaptor protein APS, Src family kinases, and Shp2 tyrosyl phosphatase bind to phosphotyrosine 568. Phosphotyrosine 82-97 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 49-53 15940693-9 2005 The p.L43F mutation belongs to a rare class of PTPN11 mutations altering the phosphotyrosine-binding region. Phosphotyrosine 77-92 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 47-53 15031289-5 2004 Shp2 was able to dephosphorylate fibroblast growth factor receptor-induced phosphotyrosines on Spry both in vivo and in vitro. Phosphotyrosine 75-91 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 0-4 15574420-2 2005 Substrate trapping experiments now suggest that SHP2 dephosphorylates other Gab1 phosphotyrosines located within a central region displaying four YXXP motifs. Phosphotyrosine 81-97 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 48-52 15289498-5 2004 Evidence is provided that the beta1 cytodomain plays an important role in mediating beta1 integrin association with either IRS-1 or Grb2-associated binder1 (Gab1)/SH2-containing protein-tyrosine phosphate 2 (Shp2), downstream effectors of IGF-IR: specifically, beta1A associates with IRS-1 and beta1C with Gab1/Shp2. Phosphotyrosine 186-204 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 208-212 15289498-5 2004 Evidence is provided that the beta1 cytodomain plays an important role in mediating beta1 integrin association with either IRS-1 or Grb2-associated binder1 (Gab1)/SH2-containing protein-tyrosine phosphate 2 (Shp2), downstream effectors of IGF-IR: specifically, beta1A associates with IRS-1 and beta1C with Gab1/Shp2. Phosphotyrosine 186-204 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 311-315 14508511-2 2003 Effector proteins that are key mediators of the ERK and PI3K pathways, namely Grb2, the tyrosine phosphatase, SHP2 and PI3K, interact with the two phosphotyrosines found in the bidentate motif in the carboxy-terminal region of V-SEA. Phosphotyrosine 147-163 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 110-114 14701753-9 2004 Moreover, SHP-2 C459S-expressing cells displayed higher Gab1 phosphotyrosine content, suggesting that SHP-2 regulates Gab1 phosphorylation through its phosphatase domain, which confers a negative regulatory effect on NF-kappaB activity. Phosphotyrosine 61-76 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 10-15 14701753-9 2004 Moreover, SHP-2 C459S-expressing cells displayed higher Gab1 phosphotyrosine content, suggesting that SHP-2 regulates Gab1 phosphorylation through its phosphatase domain, which confers a negative regulatory effect on NF-kappaB activity. Phosphotyrosine 61-76 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 102-107 14652006-0 2003 Characterization of phosphotyrosine binding motifs in the cytoplasmic domain of B and T lymphocyte attenuator required for association with protein tyrosine phosphatases SHP-1 and SHP-2. Phosphotyrosine 20-35 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 180-185 11323411-0 2001 Phosphotyrosines 627 and 659 of Gab1 constitute a bisphosphoryl tyrosine-based activation motif (BTAM) conferring binding and activation of SHP2. Phosphotyrosine 0-16 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 140-144 12482860-5 2003 In addition, the C-SH2 domain of SHP-1 has a different orientation from and is more flexible than that of SHP-2, which enables us to propose an enzymatic activation mechanism in which the C-SH2 domains of SHPs could be involved in searching for phosphotyrosine activators. Phosphotyrosine 245-260 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 106-111 12535670-2 2003 Platelet-endothelial cell adhesion molecule-1, PECAM-1, a transmembrane endothelial adhesion protein, binds and activates the tyrosine phosphatase SHP-2 via phosphotyrosines 663 and 686. Phosphotyrosine 157-173 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 147-152 12535670-5 2003 Overexpression of native PECAM-1 slowed, and nonphosphorylatable PECAM-1 increased, endothelial migration, implying that the SHP-2-regulatory phosphotyrosines negatively regulate migration. Phosphotyrosine 142-158 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 125-130 11737239-3 2001 Their phosphotyrosine-containing motifs become binding sites for Src homology 2 (SH2) domains on proteins such as SH2 domain-containing protein-tyrosine-phosphatase (SHP)-2/Syp, growth factor receptor bound-2 protein, (Grb-2), and phosphatidyl inositol 3 kinase (PI3 kinase), which participate in activation of specific signaling cascades. Phosphotyrosine 6-21 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 114-172 11684012-0 2001 Site-specific incorporation of a phosphotyrosine mimetic reveals a role for tyrosine phosphorylation of SHP-2 in cell signaling. Phosphotyrosine 33-48 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 104-109 11684012-2 2001 Using "expressed protein ligation", nonhydrolyzable phosphotyrosine analogs were introduced at known phosphorylation sites in SHP-2. Phosphotyrosine 52-67 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 126-131 11341829-4 2001 This led to the discovery of a novel phosphotyrosine bioisostere, 2-carboxymethoxybenzoic acid, and to analogues that were >100-fold more potent than the CCK-8 analogues and >10-fold selective for PTP1B over two other PTP enzymes (LAR and SHP-2), a dual specificity phosphatase (cdc25b), and a serine/threonine phosphatase (calcineurin). Phosphotyrosine 37-52 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 245-250 12731888-2 2003 In the past, expressed protein ligation has been used to site-specifically incorporate the phosphotyrosine mimic Pmp (phosphonomethylene phenylalanine) into the two tyrosine phosphorylation sites (542, 580) of SHP-2 one at a time to analyze the effects on catalytic behavior. Phosphotyrosine 91-106 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 210-215 12731888-9 2003 This allowed for a systematic analysis of intermolecular autodephosphorylation of SHP-2, which revealed how conformational plasticity can modulate phosphotyrosine stability. Phosphotyrosine 147-162 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 82-87 11323411-5 2001 Far Western blot analysis suggested that the tandem SH2 domains of SHP2 bind to Gab1 in a specific orientation, in which the N-SH2 domain binds to phosphotyrosine (Tyr(P))-627 and the C-SH2 domain binds to Tyr(P)-659. Phosphotyrosine 147-162 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 67-71 11342028-3 2001 We show here using BIAcore studies, wherein binding of peptides to SHP-2 was detected, that peptides corresponding to sequences containing phosphotyrosines 974 and 986 (LR974P and LR986P, respectively) from the leptin receptor cytoplasmic domain were the only two peptides that bound to the enzyme. Phosphotyrosine 139-155 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 67-72 11342028-9 2001 These data support a model in which SHP-2 binds to phosphotyrosine 986 in the activated leptin receptor and is activated to dephosphorylate phosphotyrosine 974, downregulating signalling events emanating from SH2 domain-containing proteins that bind here. Phosphotyrosine 51-66 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 36-41 11342028-9 2001 These data support a model in which SHP-2 binds to phosphotyrosine 986 in the activated leptin receptor and is activated to dephosphorylate phosphotyrosine 974, downregulating signalling events emanating from SH2 domain-containing proteins that bind here. Phosphotyrosine 140-155 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 36-41 10946280-8 2000 Interestingly, one SHP2-recruiting phosphotyrosine motif in a single chain of the gp130 dimer is sufficient to mediate SHP2 association to the gp130 receptor subunit and its tyrosine phosphorylation as well as to attenuate IL-6-dependent gene induction. Phosphotyrosine 35-50 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 19-23 10946280-8 2000 Interestingly, one SHP2-recruiting phosphotyrosine motif in a single chain of the gp130 dimer is sufficient to mediate SHP2 association to the gp130 receptor subunit and its tyrosine phosphorylation as well as to attenuate IL-6-dependent gene induction. Phosphotyrosine 35-50 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 119-123 10521483-4 1999 Using this approach, we demonstrate that five molecules, Grb2, Grb7, Grb14, Shp2, and the p85 subunit of phosphatidylinositol 3-kinase can interact with Tek in a phosphotyrosine-dependent manner through their SH2 domains. Phosphotyrosine 162-177 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 76-80 10829066-3 2000 The only high-affinity ligand found corresponded to the region of gp130 centered around phosphotyrosine-757 (pY757), previously shown to be a docking site for the tyrosine phosphatase SHP-2. Phosphotyrosine 88-103 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 184-189 10742110-1 2000 The tyrosine phosphatase Shp2 is recruited into tyrosine-kinase signalling pathways through binding of its two amino-terminal SH2 domains to specific phosphotyrosine motifs, concurrent with its re-localization and stimulation of phosphatase activity. Phosphotyrosine 150-165 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 25-29 10742110-10 2000 Thus, Shp2 regulates phosphotyrosine-signalling events during the complex ectodermal-mesenchymal interactions that regulate mammalian budding morphogenesis. Phosphotyrosine 21-36 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 6-10 10623804-2 2000 In vitro peptide binding experiments using phosphotyrosine-containing sequences derived from the immunoreceptor tyrosine-based inhibitory motif (ITIM) known to mediate Fc gamma RIIB1 effects suggest that the receptor uses SH2-containing inositol phosphatase (SHIP) and SH2-containing phosphotyrosine phosphatase (SHP)-1, as well as SHP-2 as effectors. Phosphotyrosine 43-58 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 332-337 8810330-7 1996 Bisphosphotyrosyl peptides corresponding to BIT-TAMs stimulated SH-PTP2 activity 33-35-fold in vitro, indicating that two SH2 domains of SH-PTP2 simultaneously interact with two phosphotyrosines of BIT-TAM. Phosphotyrosine 178-194 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 64-71 10407071-10 1999 These findings indicate that amphiphilic and hydrophilic PTPases different from PTP1B, PTP1C, PTP1D or RPTPalpha, with higher sedimentation coefficients and with higher activity when O-phosphotyrosine or a synthetic peptide phosphorylated on tyrosine were used as substrates, are present in platelets. Phosphotyrosine 183-200 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 94-99 10206955-7 1999 The first CD33 phosphotyrosine motif is dominant in CD33-SHP-1/SHP-2 interactions, since mutating tyrosine 340 in a CD33-cytoplasmic tail fusion protein significantly reduced binding to SHP-1 and SHP-2 in THP-1 lysates, while mutation of tyrosine 358 had no effect. Phosphotyrosine 15-30 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 63-68 10206955-7 1999 The first CD33 phosphotyrosine motif is dominant in CD33-SHP-1/SHP-2 interactions, since mutating tyrosine 340 in a CD33-cytoplasmic tail fusion protein significantly reduced binding to SHP-1 and SHP-2 in THP-1 lysates, while mutation of tyrosine 358 had no effect. Phosphotyrosine 15-30 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 196-201 9312087-0 1997 Characterization of phosphotyrosine binding motifs in the cytoplasmic domain of platelet/endothelial cell adhesion molecule-1 (PECAM-1) that are required for the cellular association and activation of the protein-tyrosine phosphatase, SHP-2. Phosphotyrosine 20-35 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 235-240 9254654-8 1997 The association of SHPTP2 with IL-5betacR was reconstituted using a synthetic phosphotyrosine-containing peptide, betac 605-624, encompassing tyrosine (Y)612. Phosphotyrosine 78-93 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 19-25 8810330-7 1996 Bisphosphotyrosyl peptides corresponding to BIT-TAMs stimulated SH-PTP2 activity 33-35-fold in vitro, indicating that two SH2 domains of SH-PTP2 simultaneously interact with two phosphotyrosines of BIT-TAM. Phosphotyrosine 178-194 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 137-144 7691811-0 1993 Activation of the SH2-containing phosphotyrosine phosphatase SH-PTP2 by its binding site, phosphotyrosine 1009, on the human platelet-derived growth factor receptor. Phosphotyrosine 33-48 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 61-68 7935386-10 1994 Furthermore, these results are consistent with the notion that SH-PTP2 may bind to IRS-1 through its SH2 domains in response to insulin and dephosphorylate the phosphotyrosine residue to which it binds, thereby regulating its association with IRS-1. Phosphotyrosine 160-175 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 63-70 7513703-0 1994 Activation of the SH2-containing protein tyrosine phosphatase, SH-PTP2, by phosphotyrosine-containing peptides derived from insulin receptor substrate-1. Phosphotyrosine 75-90 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 63-70 8144631-11 1994 Comparisons between peptide sequences suggest that the N-terminal SH2 domain of SH-PTP2 binds with highest affinity to phosphotyrosine (pY) followed by a beta-branched residue (Val, Ile, Thr) at pY+1 and a hydrophobic residue (Val, Leu, Ile) at pY+3 positions. Phosphotyrosine 119-134 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 80-87 8144631-11 1994 Comparisons between peptide sequences suggest that the N-terminal SH2 domain of SH-PTP2 binds with highest affinity to phosphotyrosine (pY) followed by a beta-branched residue (Val, Ile, Thr) at pY+1 and a hydrophobic residue (Val, Leu, Ile) at pY+3 positions. Phosphotyrosine 136-138 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 80-87 7691811-6 1993 Using a peptide competition assay, we now demonstrate that the major binding site for SH-PTP2 on the platelet-derived growth factor receptor is phosphotyrosine 1009. Phosphotyrosine 144-159 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 86-93 34734802-1 2021 A large number of inhibitory receptors recruit SHP1 and/or SHP2, tandem-SH2-containing phosphatases, through phosphotyrosine-based motifs ITIM and ITSM. Phosphotyrosine 109-124 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 59-63 7681589-7 1993 The structural similarity between PTP2C and the previously described PTP1C suggests the existence of a subfamily of SH2-containing PTPs; these may play an important role in signal transduction through interaction of their SH2 domains with phosphotyrosine-containing proteins. Phosphotyrosine 239-254 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 34-39 35563185-1 2022 The localization and activity of the SHP2 tyrosine phosphatase across different cellular compartments to the target substrates are steered by the binding of phosphotyrosine (pY) peptides to the tandem SH2 domains. Phosphotyrosine 157-172 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 37-41 35563185-1 2022 The localization and activity of the SHP2 tyrosine phosphatase across different cellular compartments to the target substrates are steered by the binding of phosphotyrosine (pY) peptides to the tandem SH2 domains. Phosphotyrosine 174-176 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 37-41 33043190-2 2020 Based on our previous reports that showed the importance of acidic residues surrounding SHP2 substrate phosphotyrosines for specific recognition, we have rationally designed and chemically synthesized a small-molecule SHP2 inhibitor named 4,4"-(4"-carboxy)-4-nonyloxy-[1,1"-biphenyl]-3,5-diyl)dibutanoic acid (CNBDA). Phosphotyrosine 103-119 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 88-92 34025932-0 2021 Phosphotyrosine couples peptide binding and SHP2 activation via a dynamic allosteric network. Phosphotyrosine 0-15 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 44-48 34025932-1 2021 SHP2 is a ubiquitous protein tyrosine phosphatase, whose activity is regulated by phosphotyrosine (pY)-containing peptides generated in response to extracellular stimuli. Phosphotyrosine 82-97 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 0-4 34025932-1 2021 SHP2 is a ubiquitous protein tyrosine phosphatase, whose activity is regulated by phosphotyrosine (pY)-containing peptides generated in response to extracellular stimuli. Phosphotyrosine 99-101 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 0-4 33755016-4 2021 Remarkably, in addition to newly identified substrate sites on proteins such as occludin, ARHGAP35, and PLCgamma2, another class of sites shows reduced phosphotyrosine abundance upon SHP2 inhibition. Phosphotyrosine 152-167 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 183-187 33755016-5 2021 Sites of decreased phospho-abundance are enriched on proteins with two nearby phosphotyrosine residues, which can be directly protected from dephosphorylation by the paired SH2 domains of SHP2 itself. Phosphotyrosine 78-93 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 188-192 33043190-2 2020 Based on our previous reports that showed the importance of acidic residues surrounding SHP2 substrate phosphotyrosines for specific recognition, we have rationally designed and chemically synthesized a small-molecule SHP2 inhibitor named 4,4"-(4"-carboxy)-4-nonyloxy-[1,1"-biphenyl]-3,5-diyl)dibutanoic acid (CNBDA). Phosphotyrosine 103-119 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 218-222 26359300-6 2015 Knockdown of endogenous SHP2 and reconstitution with an SHP2 mutant with impaired phosphotyrosine binding ability eliminated the EGF-mediated EMT augmentation that was otherwise restored with wild-type SHP2 reconstitution. Phosphotyrosine 82-97 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 56-60 32395997-5 2020 Association of the N-SH2 domain with binding partners containing short amino acid motifs comprising a phosphotyrosine residue (pY) leads to N-SH2/PTP dissociation and SHP2 activation. Phosphotyrosine 102-117 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 167-171 30308182-6 2018 The dephosphorylation of phosphotyrosine residues by SHP-1/SHP-2 leads to inhibition of c-Kit proliferative signaling. Phosphotyrosine 25-40 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 59-64 28912526-6 2017 Our data show that the PTPN11 tyrosine phosphatase acts as a scaffold to bridge the association between GRB2 and MPZL1 in a phosphotyrosine-dependent manner. Phosphotyrosine 124-139 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 23-29 32024694-4 2020 In this report, we show that SHP2-targeted pTyr residues exist in a specific amino acid context that allows selective binding. Phosphotyrosine 43-47 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 29-33 30308182-5 2018 Predominantly, the phosphotyrosine 568 (pY568) in Juxtamembrane (JM) region of c-Kit interacts with adaptor protein APS, Src family kinase, and SHP-2, while phosphotyrosine 570 (pY570) interacts with the SHP-1 and the adaptor protein Shc. Phosphotyrosine 19-34 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 144-149 26359300-6 2015 Knockdown of endogenous SHP2 and reconstitution with an SHP2 mutant with impaired phosphotyrosine binding ability eliminated the EGF-mediated EMT augmentation that was otherwise restored with wild-type SHP2 reconstitution. Phosphotyrosine 82-97 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 56-60 26191366-5 2015 Crystal structure analysis of SHP2 interaction with cefsulodin identified sulfophenyl acetic amide (SPAA) as a novel phosphotyrosine (pTyr) mimetic. Phosphotyrosine 117-132 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 30-34 26191366-5 2015 Crystal structure analysis of SHP2 interaction with cefsulodin identified sulfophenyl acetic amide (SPAA) as a novel phosphotyrosine (pTyr) mimetic. Phosphotyrosine 134-138 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 30-34 24632723-7 2014 Our results collectively indicate that SHP-2 alters Src kinase activity by interfering with the complex formation between CSK and phosphotyrosine caveolin-1 in the presence of H2O2, thus functions as a positive regulator in Src signaling under oxidative stress in brain astrocytes. Phosphotyrosine 130-145 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 39-44 22589543-5 2012 In addition, it binds SHP-1 and SHP-2 phosphatases in a phosphotyrosine-dependent manner, facilitating their recruitment to the plasma membrane. Phosphotyrosine 56-71 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 32-37 23792876-4 2013 Here we show that cis-interactions between the C-terminal phosphotyrosines and SH2 domain within the protein tyrosine phosphatase Shp2 can be tuned by an adaptor protein, Grb2. Phosphotyrosine 58-74 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 130-134 21193311-1 2011 Shp2 protein tyrosine phosphate (PTP) is a novel target for anticancer drug discovery. Phosphotyrosine 13-31 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 0-4 19948503-5 2009 SHP-1/SHP-2/c-Src binding was monitored by coimmunoprecipitation and phosphotyrosine-induced recruitment to CEACAM1-L in cellular monolayers. Phosphotyrosine 69-84 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 6-11 19661287-6 2009 Finally, we developed a structural model of OX1R showing that the spatial localization of phosphotyrosines in ITSM and ITIM in OX1R is compatible with their interaction with the two SH2 domains of SHP-2. Phosphotyrosine 90-106 protein tyrosine phosphatase non-receptor type 11 Homo sapiens 197-202