This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Itoh, M.
Right arrow Articles by Hirano, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Itoh, M.
Right arrow Articles by Hirano, T.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, May 2000, p. 3695-3704, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Role of Gab1 in Heart, Placenta, and Skin Development and Growth Factor- and Cytokine-Induced Extracellular Signal-Regulated Kinase Mitogen-Activated Protein Kinase Activation

Motoyuki Itoh,dagger Yuichi Yoshida, Keigo Nishida, Masahiro Narimatsu, Masahiko Hibi, and Toshio Hirano*

Division of Molecular Oncology, Biomedical Research Center, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan

Received 18 October 1999/Returned for modification 23 November 1999/Accepted 11 February 2000

Gab1 is a member of the Gab/DOS (Daughter of Sevenless) family of adapter molecules, which contain a pleckstrin homology (PH) domain and potential binding sites for SH2 and SH3 domains. Gab1 is tyrosine phosphorylated upon stimulation of various cytokines, growth factors, and antigen receptors in cell lines and interacts with signaling molecules, such as SHP-2 and phosphatidylinositol 3-kinase, although its biological roles have not yet been established. To reveal the functions of Gab1 in vivo, we generated mice lacking Gab1 by gene targeting. Gab1-deficient embryos died in utero and displayed developmental defects in the heart, placenta, and skin, which were similar to phenotypes observed in mice lacking signals of the hepatocyte growth factor/scatter factor, platelet-derived growth factor, and epidermal growth factor pathways. Consistent with these observations, extracellular signal-regulated kinase mitogen-activated protein (ERK MAP) kinases were activated at much lower levels in cells from Gab1-deficient embryos in response to these growth factors or to stimulation of the cytokine receptor gp130. These results indicate that Gab1 is a common player in a broad range of growth factor and cytokine signaling pathways linking ERK MAP kinase activation.

* Corresponding author. Mailing address: Division of Molecular Oncology (C7), Biomedical Research Center, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan. Phone: 81-6-6879-3880. Fax: 81-6-6879-3889. E-mail: hirano{at}molonc.med.osaka-u.ac.jp.

dagger Present address: Unit on Vertebrate Neural Development, Laboratory of Molecular Genetics, NICHD/NIH, Bethesda, MD 20892.

Molecular and Cellular Biology, May 2000, p. 3695-3704, Vol. 20, No. 10
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Eulenfeld, R., Schaper, F. (2009). A new mechanism for the regulation of Gab1 recruitment to the plasma membrane. J. Cell Sci. 122: 55-64 [Abstract] [Full Text]  
  • Koyama, T., Nakaoka, Y., Fujio, Y., Hirota, H., Nishida, K., Sugiyama, S., Okamoto, K., Yamauchi-Takihara, K., Yoshimura, M., Mochizuki, S., Hori, M., Hirano, T., Mochizuki, N. (2008). Interaction of Scaffolding Adaptor Protein Gab1 with Tyrosine Phosphatase SHP2 Negatively Regulates IGF-I-dependent Myogenic Differentiation via the ERK1/2 Signaling Pathway. J. Biol. Chem. 283: 24234-24244 [Abstract] [Full Text]  
  • Sampaio, C., Dance, M., Montagner, A., Edouard, T., Malet, N., Perret, B., Yart, A., Salles, J.-P., Raynal, P. (2008). Signal Strength Dictates Phosphoinositide 3-Kinase Contribution to Ras/Extracellular Signal-Regulated Kinase 1 and 2 Activation via Differential Gab1/Shp2 Recruitment: Consequences for Resistance to Epidermal Growth Factor Receptor Inhibition. Mol. Cell. Biol. 28: 587-600 [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]  
  • Zhang, Y., Diaz-Flores, E., Li, G., Wang, Z., Kang, Z., Haviernikova, E., Rowe, S., Qu, C.-K., Tse, W., Shannon, K. M., Bunting, K. D. (2007). Abnormal hematopoiesis in Gab2 mutant mice. Blood 110: 116-124 [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]  
  • Kiyatkin, A., Aksamitiene, E., Markevich, N. I., Borisov, N. M., Hoek, J. B., Kholodenko, B. N. (2006). Scaffolding Protein Grb2-associated Binder 1 Sustains Epidermal Growth Factor-induced Mitogenic and Survival Signaling by Multiple Positive Feedback Loops. J. Biol. Chem. 281: 19925-19938 [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]  
  • Parry, R. V., Whittaker, G. C., Sims, M., Edmead, C. E., Welham, M. J., Ward, S. G. (2006). Ligation of CD28 Stimulates the Formation of a Multimeric Signaling Complex Involving Grb-2-Associated Binder 2 (Gab2), Src Homology Phosphatase-2, and Phosphatidylinositol 3-Kinase: Evidence That Negative Regulation of CD28 Signaling Requires the Gab2 Pleckstrin Homology Domain. J. Immunol. 176: 594-602 [Abstract] [Full Text]  
  • Mao, Y., Lee, A. W.-M. (2005). A novel role for Gab2 in bFGF-mediated cell survival during retinoic acid-induced neuronal differentiation. JCB 170: 305-316 [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]  
  • Basar, T., Shen, Y., Ireton, K. (2005). Redundant Roles for Met Docking Site Tyrosines and the Gab1 Pleckstrin Homology Domain in InlB-Mediated Entry of Listeria monocytogenes. Infect. Immun. 73: 2061-2074 [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]  
  • Shimizu, Y., Thumkeo, D., Keel, J., Ishizaki, T., Oshima, H., Oshima, M., Noda, Y., Matsumura, F., Taketo, M. M., Narumiya, S. (2005). ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles. JCB 168: 941-953 [Abstract] [Full Text]  
  • Parekh, V., McEwen, A., Barbour, V., Takahashi, Y., Rehg, J. E., Jane, S. M., Cunningham, J. M. (2004). Defective Extraembryonic Angiogenesis in Mice Lacking LBP-1a, a Member of the grainyhead Family of Transcription Factors. Mol. Cell. Biol. 24: 7113-7129 [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]  
  • van den Akker, E., van Dijk, T., Parren-van Amelsvoort, M., Grossmann, K. S., Schaeper, U., Toney-Earley, K., Waltz, S. E., Lowenberg, B., von Lindern, M. (2004). Tyrosine kinase receptor RON functions downstream of the erythropoietin receptor to induce expansion of erythroid progenitors. Blood 103: 4457-4465 [Abstract] [Full Text]  
  • 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]  
  • Kallin, A., Demoulin, J.-B., Nishida, K., Hirano, T., Ronnstrand, L., Heldin, C.-H. (2004). Gab1 Contributes to Cytoskeletal Reorganization and Chemotaxis in Response to Platelet-derived Growth Factor. J. Biol. Chem. 279: 17897-17904 [Abstract] [Full Text]  
  • Jackson, J. G., St. Clair, P., Sliwkowski, M. X., Brattain, M. G. (2004). Blockade of Epidermal Growth Factor- or Heregulin-Dependent ErbB2 Activation with the Anti-ErbB2 Monoclonal Antibody 2C4 Has Divergent Downstream Signaling and Growth Effects. Cancer Res. 64: 2601-2609 [Abstract] [Full Text]  
  • 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]  
  • Hong, L., Munugalavadla, V., Kapur, R. (2004). c-Kit-Mediated Overlapping and Unique Functional and Biochemical Outcomes via Diverse Signaling Pathways. Mol. Cell. Biol. 24: 1401-1410 [Abstract] [Full Text]  
  • Dixit, M., Zhuang, D., Ceacareanu, B., Hassid, A. (2003). Treatment With Insulin Uncovers the Motogenic Capacity of Nitric Oxide in Aortic Smooth Muscle Cells: Dependence on Gab1 and Gab1-SHP2 Association. Circ. Res. 93 : e113-e123 [Abstract] [Full Text]  
  • Chan, P.-C., Chen, Y.-L., Cheng, C.-H., Yu, K.-C., Cary, L. A., Shu, K.-H., Ho, W. L., Chen, H.-C. (2003). Src Phosphorylates Grb2-associated Binder 1 upon Hepatocyte Growth Factor Stimulation. J. Biol. Chem. 278: 44075-44082 [Abstract] [Full Text]  
  • Wang, Y. (2003). Fill a Gab(1) in Cardiac Hypertrophy Signaling: Search a Missing Link Between gp130 and ERK5 in Hypertrophic Remodeling in Heart. Circ. Res. 93: 186-188 [Full Text]  
  • 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]  
  • Nakaoka, Y., Nishida, K., Fujio, Y., Izumi, M., Terai, K., Oshima, Y., Sugiyama, S., Matsuda, S., Koyasu, S., Yamauchi-Takihara, K., Hirano, T., Kawase, I., Hirota, H. (2003). Activation of gp130 Transduces Hypertrophic Signal Through Interaction of Scaffolding/Docking Protein Gab1 With Tyrosine Phosphatase SHP2 in Cardiomyocytes. Circ. Res. 93: 221-229 [Abstract] [Full Text]  
  • Thumkeo, D., Keel, J., Ishizaki, T., Hirose, M., Nonomura, K., Oshima, H., Oshima, M., Taketo, M. M., Narumiya, S. (2003). Targeted Disruption of the Mouse Rho-Associated Kinase 2 Gene Results in Intrauterine Growth Retardation and Fetal Death. Mol. Cell. Biol. 23: 5043-5055 [Abstract] [Full Text]  
  • Holgado-Madruga, M., Wong, A. J. (2003). Gab1 Is an Integrator of Cell Death versus Cell Survival Signals in Oxidative Stress. Mol. Cell. Biol. 23: 4471-4484 [Abstract] [Full Text]  
  • 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]  
  • 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]  
  • Kim, S.-O., Loesch, K., Wang, X., Jiang, J., Mei, L., Cunnick, J. M., Wu, J., Frank, S. J. (2002). A Role for Grb2-Associated Binder-1 in Growth Hormone Signaling. Endocrinology 143: 4856-4867 [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]  
  • LIU, F., SCHAPHORST, K. L., VERIN, A. D., JACOBS, K., BIRUKOVA, A., DAY, R. M., BOGATCHEVA, N., BOTTARO, D. P., GARCIA, J. G. N. (2002). Hepatocyte growth factor enhances endothelial cell barrier function and cortical cytoskeletal rearrangement: potential role of glycogen synthase kinase-3{beta}. FASEB J. 16: 950-962 [Abstract] [Full Text]  
  • Saito, Y., Hojo, Y., Tanimoto, T., Abe, J.-i., Berk, B. C. (2002). Protein Kinase C-alpha and Protein Kinase C-epsilon Are Required for Grb2-associated Binder-1 Tyrosine Phosphorylation in Response to Platelet-derived Growth Factor. J. Biol. Chem. 277: 23216-23222 [Abstract] [Full Text]  
  • Bourgin, C., Bourette, R. P., Arnaud, S., Liu, Y., Rohrschneider, L. R., Mouchiroud, G. (2002). Induced Expression and Association of the Mona/Gads Adapter and Gab3 Scaffolding Protein during Monocyte/Macrophage Differentiation. Mol. Cell. Biol. 22: 3744-3756 [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]  
  • Xie, Z.-H., Ambudkar, I., Siraganian, R. P. (2002). The Adapter Molecule Gab2 Regulates Fc{epsilon}RI-Mediated Signal Transduction in Mast Cells. J. Immunol. 168: 4682-4691 [Abstract] [Full Text]  
  • Nishida, K., Wang, L., Morii, E., Park, S. J., Narimatsu, M., Itoh, S., Yamasaki, S., Fujishima, M., Ishihara, K., Hibi, M., Kitamura, Y., Hirano, T. (2002). Requirement of Gab2 for mast cell development and KitL/c-Kit signaling. Blood 99: 1866-1869 [Abstract] [Full Text]  
  • Wolf, I., Jenkins, B. J., Liu, Y., Seiffert, M., Custodio, J. M., Young, P., Rohrschneider, L. R. (2002). Gab3, a New DOS/Gab Family Member, Facilitates Macrophage Differentiation. Mol. Cell. Biol. 22: 231-244 [Abstract] [Full Text]  
  • Nakae, J., Kido, Y., Accili, D. (2001). Distinct and Overlapping Functions of Insulin and IGF-I Receptors. Endocr. Rev. 22: 818-835 [Abstract] [Full Text]  
  • Kameda, H., Risinger, J. I., Han, B.-B., Baek, S. J., Barrett, J. C., Abe, T., Takeuchi, T., Glasgow, W. C., Eling, T. E. (2001). Expression of Gab1 Lacking the Pleckstrin Homology Domain Is Associated with Neoplastic Progression. Mol. Cell. Biol. 21: 6895-6905 [Abstract] [Full Text]  
  • Kameda, H., Risinger, J. I., Han, B.-B., Baek, S. J., Barrett, J. C., Glasgow, W. C., Eling, T. E. (2001). Identification of Epidermal Growth Factor Receptor- Grb2-associated Binder-1-SHP-2 Complex Formation and Its Functional Loss during Neoplastic Cell Progression. Cell Growth Differ. 12: 307-318 [Abstract] [Full Text]  
  • Liu, Y., Jenkins, B., Shin, J. L., Rohrschneider, L. R. (2001). Scaffolding Protein Gab2 Mediates Differentiation Signaling Downstream of Fms Receptor Tyrosine Kinase. Mol. Cell. Biol. 21: 3047-3056 [Abstract] [Full Text]  
  • Kido, Y., Nakae, J., Accili, D. (2001). The Insulin Receptor and Its Cellular Targets. J. Clin. Endocrinol. Metab. 86: 972-979 [Abstract] [Full Text]  
  • Lee, A. W.-M., States, D. J. (2000). Both Src-Dependent and -Independent Mechanisms Mediate Phosphatidylinositol 3-Kinase Regulation of Colony-Stimulating Factor 1-Activated Mitogen-Activated Protein Kinases in Myeloid Progenitors. Mol. Cell. Biol. 20: 6779-6798 [Abstract] [Full Text]  
  • Yart, A., Laffargue, M., Mayeux, P., Chretien, S., Peres, C., Tonks, N., Roche, S., Payrastre, B., Chap, H., Raynal, P. (2001). A Critical Role for Phosphoinositide 3-Kinase Upstream of Gab1 and SHP2 in the Activation of Ras and Mitogen-activated Protein Kinases by Epidermal Growth Factor. J. Biol. Chem. 276: 8856-8864 [Abstract] [Full Text]  
  • Craddock, B. L., Hobbs, J., Edmead, C. E., Welham, M. J. (2001). Phosphoinositide 3-Kinase-dependent Regulation of Interleukin-3-induced Proliferation. INVOLVEMENT OF MITOGEN-ACTIVATED PROTEIN KINASES, SHP2 AND Gab2. J. Biol. Chem. 276: 24274-24283 [Abstract] [Full Text]  
  • Ingham, R. J., Santos, L., Dang-Lawson, M., Holgado-Madruga, M., Dudek, P., Maroun, C. R., Wong, A. J., Matsuuchi, L., Gold, M. R. (2001). The Gab1 Docking Protein Links the B Cell Antigen Receptor to the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway and to the SHP2 Tyrosine Phosphatase. J. Biol. Chem. 276: 12257-12265 [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]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»