Essential Role of Gab1 for Signaling by the c-Met Receptor In Vivo

doi:10.1083/jcb.150.6.1375

Published online 18 September 2000. doi:10.1083/jcb.150.6.1375

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© The Rockefeller University Press, 0021-9525/2000/9/1375/ $5.00
The Journal of Cell Biology, Volume 150, Number 6, September 18, 2000 1375-1384

Original Article

Essential Role of Gab1 for Signaling by the c-Met Receptor In Vivo

Martin Sachs^a, Henning Brohmann^b, Dietmar Zechner^a, Thomas Müller^b, Jörg Hülsken^a, Ingrid Walther^a, Ute Schaeper^a, Carmen Birchmeier^b, and Walter Birchmeier^a
^a Department of Growth and Differentiation, Max-Delbrueck-Center for Molecular Medicine, 13092 Berlin, Germany
^b Department of Medical Genetics, Max-Delbrueck-Center for Molecular Medicine, 13092 Berlin, Germany

Correspondence to: Walter Birchmeier, Max-Delbrueck-Center for Molecular Medicine, Robert-Roessle-Strasse 10, 13092 Berlin, Germany. Tel:49-30-9406-3810 Fax:49-30-9406-2656

The docking protein Gab1 binds phosphorylated c-Met receptortyrosine kinase directly and mediates signals of c-Met in cellculture. Gab1 is phosphorylated by c-Met and by other receptorand nonreceptor tyrosine kinases. Here, we report the functionalanalysis of Gab1 by targeted mutagenesis in the mouse, and comparethe phenotypes of the Gab1 and c-Met mutations. Gab1 is essentialfor several steps in development: migration of myogenic precursorcells into the limb anlage is impaired in Gab1-/- embryos. Asa consequence, extensor muscle groups of the forelimbs are virtuallyabsent, and the flexor muscles reach less far. Fewer hindlimbmuscles exist, which are smaller and disorganized. Muscles inthe diaphragm, which also originate from migratory precursors,are missing. Moreover, Gab1-/- embryos die in a broad time windowbetween E13.5 and E18.5, and display reduced liver size andplacental defects. The labyrinth layer, but not the spongiotrophoblastlayer, of the placenta is severely reduced, resulting in impairedcommunication between maternal and fetal circulation. Thus,extensive similarities between the phenotypes of c-Met and HGF/SFmutant mice exist, and the muscle migration phenotype is evenmore pronounced in Gab1-/-:c-Met+/- embryos. This is geneticevidence that Gab1 is essential for c-Met signaling in vivo.Analogy exists to signal transmission by insulin receptors,which require IRS1 and IRS2 as specific docking proteins.

Key Words: hepatocyte growth factor, gene targeting, migration of muscleprecursors, placenta development, liver development

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Matzke, A., Sargsyan, V., Holtmann, B., Aramuni, G., Asan, E., Sendtner, M., Pace, G., Howells, N., Zhang, W., Ponta, H., Orian-Rousseau, V. (2007). Haploinsufficiency of c-Met in cd44 / Mice Identifies a Collaboration of CD44 and c-Met In Vivo. Mol. Cell. Biol. 27: 8797-8806 [Abstract] [Full Text]
Schaeper, U., Vogel, R., Chmielowiec, J., Huelsken, J., Rosario, M., Birchmeier, W. (2007). Distinct requirements for Gab1 in Met and EGF receptor signaling in vivo. Proc. Natl. Acad. Sci. USA 104: 15376-15381 [Abstract] [Full Text]
Dance, M., Montagner, A., Yart, A., Masri, B., Audigier, Y., Perret, B., Salles, J.-P., Raynal, P. (2006). The Adaptor Protein Gab1 Couples the Stimulation of Vascular Endothelial Growth Factor Receptor-2 to the Activation of Phosphoinositide 3-Kinase. J. Biol. Chem. 281: 23285-23295 [Abstract] [Full Text]
Chen, S.-Y., Chen, H.-C. (2006). Direct Interaction of Focal Adhesion Kinase (FAK) with Met Is Required for FAK To Promote Hepatocyte Growth Factor-Induced Cell Invasion.. Mol. Cell. Biol. 26: 5155-5167 [Abstract] [Full Text]
Bard-Chapeau, E. A., Yuan, J., Droin, N., Long, S., Zhang, E. E., Nguyen, T. V., Feng, G.-S. (2006). Concerted Functions of Gab1 and Shp2 in Liver Regeneration and Hepatoprotection. Mol. Cell. Biol. 26: 4664-4674 [Abstract] [Full Text]
Brummer, T., Schramek, D., Hayes, V. M., Bennett, H. L., Caldon, C. E., Musgrove, E. A., Daly, R. J. (2006). Increased Proliferation and Altered Growth Factor Dependence of Human Mammary Epithelial Cells Overexpressing the Gab2 Docking Protein. J. Biol. Chem. 281: 626-637 [Abstract] [Full Text]
Vasyutina, E., Stebler, J., Brand-Saberi, B., Schulz, S., Raz, E., Birchmeier, C. (2005). CXCR4 and Gab1 cooperate to control the development of migrating muscle progenitor cells. Genes Dev. 19: 2187-2198 [Abstract] [Full Text]
Watson, E. D., Cross, J. C. (2005). Development of Structures and Transport Functions in the Mouse Placenta. Physiology 20: 180-193 [Abstract] [Full Text]
Jin, Z.-G., Wong, C., Wu, J., Berk, B. C. (2005). Flow Shear Stress Stimulates Gab1 Tyrosine Phosphorylation to Mediate Protein Kinase B and Endothelial Nitric-oxide Synthase Activation in Endothelial Cells. J. Biol. Chem. 280: 12305-12309 [Abstract] [Full Text]
Borowiak, M., Garratt, A. N., Wustefeld, T., Strehle, M., Trautwein, C., Birchmeier, C. (2004). Met provides essential signals for liver regeneration. Proc. Natl. Acad. Sci. USA 101: 10608-10613 [Abstract] [Full Text]
Lamothe, B., Yamada, M., Schaeper, U., Birchmeier, W., Lax, I., Schlessinger, J. (2004). 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. Mol. Cell. Biol. 24: 5657-5666 [Abstract] [Full Text]
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Podar, K., Mostoslavsky, G., Sattler, M., Tai, Y.-T., Hayashi, T., Catley, L. P., Hideshima, T., Mulligan, R. C., Chauhan, D., Anderson, K. C. (2004). Critical Role for Hematopoietic Cell Kinase (Hck)-mediated Phosphorylation of Gab1 and Gab2 Docking Proteins in Interleukin 6-induced Proliferation and Survival of Multiple Myeloma Cells. J. Biol. Chem. 279: 21658-21665 [Abstract] [Full Text]
Relaix, F., Rocancourt, D., Mansouri, A., Buckingham, M. (2004). Divergent functions of murine Pax3 and Pax7 in limb muscle development. Genes Dev. 18: 1088-1105 [Abstract] [Full Text]
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Holgado-Madruga, M., Wong, A. J. (2004). Role of the Grb2-Associated Binder 1/SHP-2 Interaction in Cell Growth and Transformation. Cancer Res. 64: 2007-2015 [Abstract] [Full Text]
Sun, Y., Yuan, J., Liu, H., Shi, Z., Baker, K., Vuori, K., Wu, J., Feng, G.-S. (2004). Role of Gab1 in UV-Induced c-Jun NH2-Terminal Kinase Activation and Cell Apoptosis. Mol. Cell. Biol. 24: 1531-1539 [Abstract] [Full Text]
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Lock, L. S., Frigault, M. M., Saucier, C., Park, M. (2003). Grb2-independent Recruitment of Gab1 Requires the C-terminal Lobe and Structural Integrity of the Met Receptor Kinase Domain. J. Biol. Chem. 278: 30083-30090 [Abstract] [Full Text]
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Gu, H., Botelho, R. J., Yu, M., Grinstein, S., Neel, B. G. (2003). Critical role for scaffolding adapter Gab2 in Fc{gamma}R-mediated phagocytosis. JCB 161: 1151-1161 [Abstract] [Full Text]
Laclef, C., Hamard, G., Demignon, J., Souil, E., Houbron, C., Maire, P. (2003). Altered myogenesis in Six1-deficient mice. Development 130: 2239-2252 [Abstract] [Full Text]
Kong, M., Mounier, C., Balbis, A., Baquiran, G., Posner, B. I. (2003). Gab2 Tyrosine Phosphorylation by a Pleckstrin Homology Domain-Independent Mechanism: Role in Epidermal Growth Factor-Induced Mitogenesis. Mol. Endocrinol. 17: 935-944 [Abstract] [Full Text]
Seiffert, M., Custodio, J. M., Wolf, I., Harkey, M., Liu, Y., Blattman, J. N., Greenberg, P. D., Rohrschneider, L. R. (2003). Gab3-Deficient Mice Exhibit Normal Development and Hematopoiesis and Are Immunocompetent. Mol. Cell. Biol. 23: 2415-2424 [Abstract] [Full Text]
Palka, H. L., Park, M., Tonks, N. K. (2003). Hepatocyte Growth Factor Receptor Tyrosine Kinase Met Is a Substrate of the Receptor Protein-tyrosine Phosphatase DEP-1. J. Biol. Chem. 278: 5728-5735 [Abstract] [Full Text]
Cai, T., Nishida, K., Hirano, T., Khavari, P. A. (2002). Gab1 and SHP-2 promote Ras/MAPK regulation of epidermal growth and differentiation. JCB 159: 103-112 [Abstract] [Full Text]
Gogg, S., Smith, U. (2002). Epidermal Growth Factor and Transforming Growth Factor alpha Mimic the Effects of Insulin in Human Fat Cells and Augment Downstream Signaling in Insulin Resistance. J. Biol. Chem. 277: 36045-36051 [Abstract] [Full Text]
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Zhang, S. Q., Tsiaras, W. G., Araki, T., Wen, G., Minichiello, L., Klein, R., Neel, B. G. (2002). Receptor-Specific Regulation of Phosphatidylinositol 3'-Kinase Activation by the Protein Tyrosine Phosphatase Shp2. Mol. Cell. Biol. 22: 4062-4072 [Abstract] [Full Text]
Lock, L. S., Maroun, C. R., Naujokas, M. A., Park, M. (2002). Distinct Recruitment and Function of Gab1 and Gab2 in Met Receptor-mediated Epithelial Morphogenesis. Mol. Biol. Cell 13: 2132-2146 [Abstract] [Full Text]
Itoh, S., Itoh, M., Nishida, K., Yamasaki, S., Yoshida, Y., Narimatsu, M., Park, S. J., Hibi, M., Ishihara, K., Hirano, T. (2002). Adapter Molecule Grb2-Associated Binder 1 Is Specifically Expressed in Marginal Zone B Cells and Negatively Regulates Thymus-Independent Antigen-2 Responses. J. Immunol. 168: 5110-5116 [Abstract] [Full Text]
Grimm, J., Sachs, M., Britsch, S., Di Cesare, S., Schwarz-Romond, T., Alitalo, K., Birchmeier, W. (2001). Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation. JCB 154: 345-354 [Abstract] [Full Text]
Yu, C. F., Roshan, B., Liu, Z.-X., Cantley, L. G. (2001). ERK Regulates the Hepatocyte Growth Factor-mediated Interaction of Gab1 and the Phosphatidylinositol 3-Kinase. J. Biol. Chem. 276: 32552-32558 [Abstract] [Full Text]
Ong, S. H., Hadari, Y. R., Gotoh, N., Guy, G. R., Schlessinger, J., Lax, I. (2001). Stimulation of phosphatidylinositol 3-kinase by fibroblast growth factor receptors is mediated by coordinated recruitment of multiple docking proteins. Proc. Natl. Acad. Sci. USA 98: 6074-6079 [Abstract] [Full Text]