Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Gab1 is required for cell cycle transition, cell proliferation, and transformation induced by an oncogenic met receptor.
Mood K
,
Saucier C
,
Bong YS
,
Lee HS
,
Park M
,
Daar IO
.
???displayArticle.abstract???
We have shown previously that either Grb2- or Shc-mediated signaling from the oncogenic Met receptor Tpr-Met is sufficient to trigger cell cycle progression in Xenopus oocytes. However, direct binding of these adaptors to Tpr-Met is dispensable, implying that another Met binding partner mediates these responses. In this study, we show that overexpression of Grb2-associated binder 1 (Gab1) promotes cell cycle progression when Tpr-Met is expressed at suboptimal levels. This response requires that Gab1 possess an intact Met-binding motif, the pleckstrin homology domain, and the binding sites for phosphatidylinositol 3-kinase and tyrosine phosphatase SHP-2, but not the Grb2 and CrkII/phospholipase Cgamma binding sites. Importantly, we establish that Gab1-mediated signals are critical for cell cycle transition promoted by the oncogenic Met and fibroblast growth factor receptors, but not by progesterone, the natural inducer of cell cycle transition in Xenopus oocytes. Moreover, Gab1 is essential for Tpr-Met-mediated morphological transformation and proliferation of fibroblasts. This study provides the first evidence that Gab1 is a key binding partner of the Met receptor for induction of cell cycle progression, proliferation, and oncogenic morphological transformation. This study identifies Gab1 and its associated signaling partners as potential therapeutic targets to impair proliferation or transformation of cancer cells in human malignancies harboring a deregulated Met receptor.
Bardelli,
Gab1 coupling to the HGF/Met receptor multifunctional docking site requires binding of Grb2 and correlates with the transforming potential.
1997, Pubmed
Bardelli,
Gab1 coupling to the HGF/Met receptor multifunctional docking site requires binding of Grb2 and correlates with the transforming potential.
1997,
Pubmed
Bardelli,
Concomitant activation of pathways downstream of Grb2 and PI 3-kinase is required for MET-mediated metastasis.
1999,
Pubmed
Birchmeier,
Met, metastasis, motility and more.
2003,
Pubmed
Bladt,
Essential role for the c-met receptor in the migration of myogenic precursor cells into the limb bud.
1995,
Pubmed
Browaeys-Poly,
Signal transduction pathways triggered by fibroblast growth factor receptor 1 expressed in Xenopus laevis oocytes after fibroblast growth factor 1 addition. Role of Grb2, phosphatidylinositol 3-kinase, Src tyrosine kinase, and phospholipase Cgamma.
2000,
Pubmed
,
Xenbase
Carballada,
Phosphatidylinositol-3 kinase acts in parallel to the ERK MAP kinase in the FGF pathway during Xenopus mesoderm induction.
2001,
Pubmed
,
Xenbase
Cooper,
Molecular cloning of a new transforming gene from a chemically transformed human cell line.
,
Pubmed
Cunnick,
Regulation of the mitogen-activated protein kinase signaling pathway by SHP2.
2002,
Pubmed
Fabian,
Requirement for Raf and MAP kinase function during the meiotic maturation of Xenopus oocytes.
1993,
Pubmed
,
Xenbase
Ferrell,
Xenopus oocyte maturation: new lessons from a good egg.
1999,
Pubmed
,
Xenbase
Fixman,
Efficient cellular transformation by the Met oncoprotein requires a functional Grb2 binding site and correlates with phosphorylation of the Grb2-associated proteins, Cbl and Gab1.
1997,
Pubmed
Fixman,
Pathways downstream of Shc and Grb2 are required for cell transformation by the tpr-Met oncoprotein.
1996,
Pubmed
Fournier,
Branching tubulogenesis but not scatter of madin-darby canine kidney cells requires a functional Grb2 binding site in the Met receptor tyrosine kinase.
1996,
Pubmed
Garcia-Guzman,
Met-induced JNK activation is mediated by the adapter protein Crk and correlates with the Gab1 - Crk signaling complex formation.
1999,
Pubmed
Gu,
The "Gab" in signal transduction.
2003,
Pubmed
Gual,
Sustained recruitment of phospholipase C-gamma to Gab1 is required for HGF-induced branching tubulogenesis.
2000,
Pubmed
Holgado-Madruga,
Grb2-associated binder-1 mediates phosphatidylinositol 3-kinase activation and the promotion of cell survival by nerve growth factor.
1997,
Pubmed
Holgado-Madruga,
A Grb2-associated docking protein in EGF- and insulin-receptor signalling.
1996,
Pubmed
Horiguchi,
Hepatocyte growth factor promotes hepatocarcinogenesis through c-Met autocrine activation and enhanced angiogenesis in transgenic mice treated with diethylnitrosamine.
2002,
Pubmed
Jeffers,
Activating mutations for the met tyrosine kinase receptor in human cancer.
1997,
Pubmed
Kamikura,
Identification of tyrosine 489 in the carboxy terminus of the Tpr-Met oncoprotein as a major site of autophosphorylation.
1996,
Pubmed
Katso,
Cellular function of phosphoinositide 3-kinases: implications for development, homeostasis, and cancer.
2001,
Pubmed
Klein,
Genetic and genomic tools for Xenopus research: The NIH Xenopus initiative.
2002,
Pubmed
,
Xenbase
Koibuchi,
Essential role of HGF (hepatocyte growth factor) in blood formation in Xenopus.
2004,
Pubmed
,
Xenbase
Lamorte,
A switch from p130Cas/Crk to Gab1/Crk signaling correlates with anchorage independent growth and JNK activation in cells transformed by the Met receptor oncoprotein.
2000,
Pubmed
Lamorte,
Crk adapter proteins promote an epithelial-mesenchymal-like transition and are required for HGF-mediated cell spreading and breakdown of epithelial adherens junctions.
2002,
Pubmed
Lamorte,
Crk synergizes with epidermal growth factor for epithelial invasion and morphogenesis and is required for the met morphogenic program.
2002,
Pubmed
Lamothe,
The docking protein Gab1 is an essential component of an indirect mechanism for fibroblast growth factor stimulation of the phosphatidylinositol 3-kinase/Akt antiapoptotic pathway.
2004,
Pubmed
Lannon,
A highly conserved NTRK3 C-terminal sequence in the ETV6-NTRK3 oncoprotein binds the phosphotyrosine binding domain of insulin receptor substrate-1: an essential interaction for transformation.
2004,
Pubmed
Lock,
Grb2-independent recruitment of Gab1 requires the C-terminal lobe and structural integrity of the Met receptor kinase domain.
2003,
Pubmed
Lock,
Identification of an atypical Grb2 carboxyl-terminal SH3 domain binding site in Gab docking proteins reveals Grb2-dependent and -independent recruitment of Gab1 to receptor tyrosine kinases.
2000,
Pubmed
Lock,
Distinct recruitment and function of Gab1 and Gab2 in Met receptor-mediated epithelial morphogenesis.
2002,
Pubmed
Ma,
c-MET mutational analysis in small cell lung cancer: novel juxtamembrane domain mutations regulating cytoskeletal functions.
2003,
Pubmed
Maroun,
A conserved inositol phospholipid binding site within the pleckstrin homology domain of the Gab1 docking protein is required for epithelial morphogenesis.
1999,
Pubmed
Maroun,
The tyrosine phosphatase SHP-2 is required for sustained activation of extracellular signal-regulated kinase and epithelial morphogenesis downstream from the met receptor tyrosine kinase.
2000,
Pubmed
Maroun,
The Gab1 PH domain is required for localization of Gab1 at sites of cell-cell contact and epithelial morphogenesis downstream from the met receptor tyrosine kinase.
1999,
Pubmed
Mood,
Oncogenic Met receptor induces cell-cycle progression in Xenopus oocytes independent of direct Grb2 and Shc binding or Mos synthesis, but requires phosphatidylinositol 3-kinase and Raf signaling.
2006,
Pubmed
,
Xenbase
Mood,
SNT1/FRS2 mediates germinal vesicle breakdown induced by an activated FGF receptor1 in Xenopus oocytes.
2002,
Pubmed
,
Xenbase
Nebreda,
Regulation of the meiotic cell cycle in oocytes.
2000,
Pubmed
,
Xenbase
Nguyen,
Association of the multisubstrate docking protein Gab1 with the hepatocyte growth factor receptor requires a functional Grb2 binding site involving tyrosine 1356.
1997,
Pubmed
Ong,
ShcA and Grb2 mediate polyoma middle T antigen-induced endothelial transformation and Gab1 tyrosine phosphorylation.
2001,
Pubmed
Park,
Mechanism of met oncogene activation.
1986,
Pubmed
Pickham,
Requirement of mosXe protein kinase for meiotic maturation of Xenopus oocytes induced by a cdc2 mutant lacking regulatory phosphorylation sites.
1992,
Pubmed
,
Xenbase
Pollack,
Morphogenetic mechanisms of epithelial tubulogenesis: MDCK cell polarity is transiently rearranged without loss of cell-cell contact during scatter factor/hepatocyte growth factor-induced tubulogenesis.
1998,
Pubmed
Ponzetto,
Specific uncoupling of GRB2 from the Met receptor. Differential effects on transformation and motility.
1996,
Pubmed
Rodrigues,
Activation of the JNK pathway is essential for transformation by the Met oncogene.
1997,
Pubmed
Rodrigues,
CrkI and CrkII function as key signaling integrators for migration and invasion of cancer cells.
2005,
Pubmed
Rodrigues,
Alternative splicing generates isoforms of the met receptor tyrosine kinase which undergo differential processing.
1991,
Pubmed
Rodrigues,
Dimerization mediated through a leucine zipper activates the oncogenic potential of the met receptor tyrosine kinase.
1993,
Pubmed
Sattler,
Critical role for Gab2 in transformation by BCR/ABL.
2002,
Pubmed
Saucier,
The Shc adaptor protein is critical for VEGF induction by Met/HGF and ErbB2 receptors and for early onset of tumor angiogenesis.
2004,
Pubmed
Saucier,
Use of signal specific receptor tyrosine kinase oncoproteins reveals that pathways downstream from Grb2 or Shc are sufficient for cell transformation and metastasis.
2002,
Pubmed
Schmidt,
Scatter factor/hepatocyte growth factor is essential for liver development.
1995,
Pubmed
Toyoda,
Overexpression of hepatocyte growth factor/scatter factor promotes vascularization and granulation tissue formation in vivo.
2001,
Pubmed
Uehara,
Placental defect and embryonic lethality in mice lacking hepatocyte growth factor/scatter factor.
1995,
Pubmed
Weidner,
Interaction between Gab1 and the c-Met receptor tyrosine kinase is responsible for epithelial morphogenesis.
1996,
Pubmed
Yu,
Hepatocyte growth factor switches orientation of polarity and mode of movement during morphogenesis of multicellular epithelial structures.
2003,
Pubmed
Zhang,
HGF/SF-met signaling in the control of branching morphogenesis and invasion.
2003,
Pubmed
