| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.86813615 |
| Here we show that Gab 1 interacts directly with the c met encoded receptor tyrosine kinase but not with a number of other tyrosine kinases from different subfamilies . 0.86813615^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.72162334 |
| Association of Gab 1 with Met requires a functional Grb 2 binding site involving tyrosine 1356 and to a lesser extent tyrosine 1349 . 0.72162334^^^ Met receptor mutants that fail to induce branching tubulogenesis are impaired in their ability to interact with Gab 1 , suggesting that Gab 1 may play a role in these processes . . 0.59551145^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.533034 |
| Gab 1 binds to c Met phosphorylated on tyrosine residues , but not to a number of other tyrosine kinases from different subfamilies . 0.533034^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.61307564 |
| Our studies show that activated Met associates with , and phosphorylates , the docking protein Gab 1 , which in turn binds to the src homology 2 ( SH 2 ) domain of the adapter protein Crk and recruits Crk to the Met signaling complex . 0.61307564^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.72210688 |
| However , the HGF receptor is the only one known to associate directly with Gab 1 . 0.72210688^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| The multisubstrate binding protein Gab 1 ( Grb 2 associated binder 1 ) is the major phosphorylated protein in epithelial cells following activation of Met . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Grb 2 associated binder 1 ( GAB 1 ) is a docking protein found to associate with the activated c MET receptor via the MET binding domain ( MBD ) and appears to be critical for the tubulogenic actions of this receptor . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| The HGF receptor directly activates PI 3 kinase , Ras and STAT signalling pathways and phosphorylates the adaptator GRB 2 Associated Binder 1 ( Gab 1 ) . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Interestingly , the expression of CD 44 HS on B cells strongly promotes HGF induced signaling , resulting in an HS dependent enhanced phosphorylation of Met , the receptor tyrosine kinase for HGF , as well as downstream signaling molecules including Grb 2 associated binder 1 ( Gab 1 ) and Akt / protein kinase B ( PKB ) . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| In a search for substrates downstream from Met , we have previously identified the Grb 2 associated binder 1 ( Gab 1 ) as critical for the morphogenic program . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| In this study , we show that overexpression of Grb 2 associated binder 1 ( Gab 1 ) promotes cell cycle progression when Tpr Met is expressed at suboptimal levels . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Here , we provide evidence that Crk adaptor protein is required for the sustained phosphorylation of c Met docking protein Grb 2 associated binder 1 ( Gab 1 ) in response to HGF , leading to the enhanced cell motility of human synovial sarcoma cell lines SYO 1 , HS SY 2 , and Fuji . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Efficient cellular transformation by the Met oncoprotein requires a functional Grb 2 binding site and correlates with phosphorylation of the Grb 2 associated proteins , Cbl and Gab 1 . ^^^ We show here that the 110 kDa Tpr Met substrate corresponds to the recently identified Grb 2 associated protein , Gab 1 . ^^^ Moreover , we show that tyrosine phosphorylation of the Cbl protooncogene product as well as Gab 1 required Tyr 489 and correlated with the ability of Tpr Met to associate with Grb 2 and to transform cells , providing evidence that pathways downstream of Gab 1 and / or Cbl may play a role in Tpr Met mediated cell transformation . . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Gab 1 coupling to the HGF / Met receptor multifunctional docking site requires binding of Grb 2 and correlates with the transforming potential . ^^^ It has recently been shown that the Met receptor interacts with Gab 1 , an IRS like adaptor protein , via the docking site ( Y1349VHVNATY1356VNV ) known to bind Grb 2 and multiple SH 2 containing signal transducers . ^^^ Here we show that Gab 1 is the major phosphorylation substrate of the Met receptor and of its oncogenic variant Tpr Met . ^^^ These data indicate that Gab 1 coupling to the Met receptor requires binding of Grb 2 and correlates with the transforming potential of Tpr Met . . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| The c met mediated response could also be evoked by transfection of a c met specific substrate , Gab 1 , which can activate the PI 3 kinase pathway . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| The Gab 1 PH domain is required for localization of Gab 1 at sites of cell cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase . ^^^ We have previously shown that Gab 1 is the major phosphorylated protein following stimulation of the Met receptor in epithelial cells that undergo a morphogenic program in response to HGF . ^^^ Met receptor mutants that are impaired in their association with Gab 1 fail to induce branching tubulogenesis . ^^^ Overexpression of Gab 1 rescues the Met dependent tubulogenic response in these cell lines . ^^^ These data show that Gab 1 is an important mediator of branching tubulogenesis downstream from the Met receptor and identify phosphatidylinositol 3 kinase and the Gab 1 pleckstrin homology domain as crucial for subcellular localization of Gab 1 and biological responses . . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Upon activation , the HGF receptor c Met binds and phosphorylates the multisite docking protein Gab 1 . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Furthermore , the multisubstrate adapter protein Gab 1 , which couples the Met receptor with PI3 ' K , enhances Met receptor dependent HA synthesis in a PI3 ' K dependent manner . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Coupling of Gab 1 to c Met , Grb 2 , and Shp 2 mediates biological responses . ^^^ Gab 1 is a substrate of the receptor tyrosine kinase c Met and involved in c Met specific branching morphogenesis . ^^^ The c Met binding site is localized to a 13 amino acid region unique to Gab 1 . ^^^ Insertion of this site into the Gab 1 related protein p97 / Gab2 was sufficient to confer c Met binding activity . ^^^ Overexpression of a Gab 1 mutant deficient in Shp 2 interaction could also block HGF / SF induced activation of the MAPK pathway , suggesting that Shp 2 is critical for c Met / Gab1 specific signaling . . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Gab 1 acts downstream from the Met hepatocyte growth factor receptor , and Gab 1 overexpression promotes Met dependent morphogenesis of epithelial cells . ^^^ Recruitment of Gab 1 to Met or epidermal growth factor ( EGF ) receptors requires a receptor binding site for the Grb 2 adapter protein and a proline rich domain in Gab 1 , defined as the Met binding domain . ^^^ One corresponds to a canonical Grb 2 binding motif , whereas the second , located within the Gab 1 Met binding domain , requires the proline and arginine residues of an atypical PXXXR motif . ^^^ The association of Gab 1 with Grb 2 is required for Gab 1 recruitment to the EGF receptor but not the Met receptor . ^^^ Hence different mechanisms of Gab 1 recruitment may reflect the distinct biological functions for Gab 1 downstream from the EGF and Met receptors . . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Following activation , Met signaling is elicited via its interactions with SH 2 containing proteins , or via the phosphorylation of the docking protein Gab 1 , and the subsequent interaction of Gab 1 with additional SH 2 containing effector molecules . ^^^ We have previously shown that the interaction between phosphorylated Gab 1 and the adaptor protein Crk mediates activation of the JNK pathway downstream of Met . ^^^ We report here that c Cbl , which is a Gab 1 like docking protein , also becomes tyrosine phosphorylated in response to Met activation and serves as a docking molecule for various SH 2 containing molecules , including Crk . ^^^ We also show that both Cbl and Gab 1 enhance Met induced activation of another MAP kinase cascade , the ERK pathway , in a Crk independent manner . ^^^ Taken together , our studies demonstrate a previously unidentified functional role for Cbl in Met signaling and suggest that Met utilizes at least two docking proteins , Gab 1 and Cbl , to activate downstream signaling pathways . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Essential role of Gab 1 for signaling by the c Met receptor in vivo . ^^^ The docking protein Gab 1 binds phosphorylated c Met receptor tyrosine kinase directly and mediates signals of c Met in cell culture . ^^^ Gab 1 is phosphorylated by c Met and by other receptor and nonreceptor tyrosine kinases . ^^^ Here , we report the functional analysis of Gab 1 by targeted mutagenesis in the mouse , and compare the phenotypes of the Gab 1 and c Met mutations . ^^^ Thus , extensive similarities between the phenotypes of c Met and HGF / SF mutant mice exist , and the muscle migration phenotype is even more pronounced in Gab 1 / : c Met+ / embryos . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Previous studies have identified Gab 1 , the major phosphorylated protein following Met activation , as important for the morphogenic response . ^^^ Gab 1 is a docking protein that couples the Met receptor with multiple signaling proteins , including phosphatidylinositol 3 kinase , phospholipase Cgamma , the adapter protein Crk , and the tyrosine specific phosphatase SHP 2 . ^^^ To elucidate the Gab 1 dependent signals required for epithelial morphogenesis , we undertook a structure function approach and demonstrate that association of Gab 1 with the tyrosine phosphatase SHP 2 is required for sustained Erk activation and for epithelial morphogenesis downstream from the Met receptor . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Gab 1 phosphorylation : a novel mechanism for negative regulation of HGF receptor signaling . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| HGF also stimulated expression and tyrosine phosphorylation of c Met and Gab 1 as well as protein kinase C ( PKC ) alpha expression . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| In support of this divergent effect of ERK on Gab1 / PI3K association following HGF and EGF stimulation , U 0126 decreased the HGF stimulated association of p 85 and the Gab 1 c Met binding domain but did not alter the EGF stimulated association of p 85 and the c Met binding domain . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Distinct recruitment and function of Gab 1 and Gab 2 in Met receptor mediated epithelial morphogenesis . ^^^ Gab 1 acts to diversify the signal downstream from the Met receptor tyrosine kinase through the recruitment of multiple signaling proteins , and is essential for epithelial morphogenesis . ^^^ In contrast , Gab 1 recruitment to Met is both Grb 2 dependent and Grb 2 independent . ^^^ The latter requires a novel amino acid sequence present in the Met binding domain of Gab 1 but not Gab 2 . ^^^ Mutation of these residues in Gab 1 impairs both association with the Met receptor and the ability of Gab 1 to promote a morphogenic response , whereas their insertion into Gab 2 increases Gab 2 association with Met , but does not confer on Gab 2 the ability to promote epithelial morphogenesis . ^^^ |
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| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| We have previously shown that the Gab 1 docking protein is required for branching morphogenesis downstream of the Met receptor . ^^^ Consistent with a role for CrkII in promoting EGF dependent branching morphogenesis , the binding of Gab 1 to CrkII is required for the branching morphogenic program downstream of Met . ^^^ |
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| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| We have shown that the substrate trapping mutant form of DEP 1 interacted with a small subset of tyrosine phosphorylated proteins from lysates of the human breast tumor cell lines MDA MB 231 , T 47D , and T 47D / Met and have identified the hepatocyte growth factor / scatter factor receptor Met , the adapter protein Gab 1 , and the junctional component p 120 catenin as potential substrates . ^^^ Furthermore , we observed that DEP 1 preferentially dephosphorylated a Gab 1 binding site ( Tyr ( 1349 ) ) and a COOH terminal tyrosine implicated in morphogenesis ( Tyr ( 1365 ) ) , whereas tyrosine residues in the activation loop of Met ( Tyr ( 1230 ) , Tyr ( 1234 ) , and Tyr ( 1235 ) ) were not preferred targets of the PTP . ^^^ |
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| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Grb 2 independent recruitment of Gab 1 requires the C terminal lobe and structural integrity of the Met receptor kinase domain . ^^^ In addition , Gab 1 interacts with the Met / hepatocyte growth factor receptor in a Grb 2 independent manner . ^^^ This interaction requires a Met binding domain ( MBD ) in Gab 1 and is essential for Met mediated epithelial morphogenesis . ^^^ The Gab 1 MBD has been proposed to act as a phosphotyrosine binding domain that binds Tyr 1349 in the Met receptor . ^^^ We show that a 16 amino acid motif within the Gab 1 MBD is sufficient for interaction with the Met receptor , suggesting that it is unlikely that the Gab 1 MBD forms a structured domain . ^^^ |
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| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| The WiT 49 cell line responded to recombinant human HGF by an increase in the expression of the met receptor , recruitment of the Gab 1 adapter protein to met and release of bound beta catenin from met . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| In addition , PHA 665752 inhibited HGF stimulated or constitutive phosphorylation of mediators of downstream signal transduction of c Met , including Gab 1 , extracellular regulated kinase , Akt , signal transducer and activator of transcription 3 , phospholipase C gamma , and focal adhesion kinase , in multiple tumor cell lines in a pattern correlating to the phenotypic response of a given tumor cell . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Genetic and pharmaceutical analyses suggest the involvement of c Met and the Src family tyrosine kinases in mediating UV induced Gab 1 phosphorylation as well as JNK activation . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| PHA 665752 inhibited phosphorylation of several tyrosine residues in c Met ( Tyr ( 1003 ) , Tyr ( 1230 / 1234 / 1235 ) , and Tyr ( 1349 ) ) , blocked HGF mediated activation of Akt and p44 / 42 mitogen activated protein kinase , and prevented the adaptor molecule Gab 1 from complexing with c Met . ^^^ |
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| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| InlB / Met interaction results in activation of the host phosphoinositide ( PI ) 3 kinase p 85 p110 , an event required for bacterial entry . p 85 p110 activation coincides with tyrosine phosphorylation of the host adaptor Gab 1 , and formation of complexes between Gab 1 and the p 85 regulatory subunit of PI 3 kinase . ^^^ |
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| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Redundant roles for Met docking site tyrosines and the Gab 1 pleckstrin homology domain in InlB mediated entry of Listeria monocytogenes . ^^^ Binding of InlB leads to phosphorylation of Met and the adapter Gab 1 and to activation of host phosphoinositide ( PI ) 3 kinase . ^^^ Surprisingly , cells expressing mutant Met containing phenylalanine substitutions in both tyrosines 1349 and 1356 ( MetYF ) allowed entry and InlB induced Gab 1 phosphorylation . ^^^ However , in contrast to the situation in cells expressing wild type Met , Gab 1 phosphorylation in MetYF cells required PI 3 kinase activity . ^^^ |
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| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Since Gab 1 , JNK and PI 3 kinase are activated with same intensity and kinetics by HGF and by the two agonist antibodies , it is concluded that level and duration of MAPK activation by Met receptor are crucial for the induction of a full HGF dependent mitogenic and invasive program in KS cells . . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| Gab 1 encodes an adaptor protein that transduces signals elicited by tyrosine kinase receptors , for instance the c Met receptor , and plays a role in the migration of muscle progenitor cells . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| HGF stimulated Gab 1 association with c Met , Grb 2 , SHP 2 , PI3K , Shc , Crk isoforms and CrkL , but not with PLCgamma 1 . ^^^ |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| NA |
|
| Interacting proteins: Q13480 and P08581 |
Pubmed |
SVM Score :0.0 |
| NA |
|