Abstract
THE protein Grb2 plays a central role in signalling by receptor protein-tyrosine kinases1,2, where its SH2 domain binds to the receptor and its two SH3 domains link to effectors. One target effector is SOS, SO Grb2 links receptor protein-tyrosine kinases with the Ras signalling pathway. The SH3 domains can also couple to other signalling proteins, including Vav3, c-Abl4 and dynamin5. We have identified several bands in glial and medullo-blastoma tumours that are recognized by Grb2 but these did not correspond to any known protein. Here we use recombinant Grb2 to isolate a complementary DNA called Gabl (for Grb2-asso-ciated binder-1). Gabl shares amino-acid homology and several structural features with IRS-1 (insulin-receptor substrate-1; refs 6,7), is a substate of the EGF and insulin receptors, and can act as a docking protein for several SH2-containing proteins. Over-expression of Gabl enhances cell growth and results in transformation. We conclude that Gabl is a new protein in EGF and insulin receptor signalling which could integrate signals from different systems.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Lowenstein, E. J. et al. Cell 70, 431–442 (1992).
Downward, J. FEBS Lett. 338, 113–117 (1994).
Ren, R., Ye, Z. S. & Baltimore, D. Genes Dev. 8, 783–795 (1994).
Ye, Z. S. & Baltimore, D. Proc. natn. Acad. Sci. U.S.A. 91, 12629–12633 (1994).
Gout, I. et al. Cell 75, 25–36 (1993).
Sun, X. J. et al. Nature 352, 73–77 (1991).
Araki, E. et al. Diabetes 42, 1041–1054 (1993).
Ron, D. & Dressler, H. Biotechniques 13, 866–869 (1992).
Musacchio, A., Gibson, T., Rice, P., Thompson, J. & Saraste, M. Trends biochem. Sci. 18, 343–348 (1993).
Skolnik, E. Y. et al. Science 260, 1953–1955 (1993).
Lee, C. H. et al. Proc. natn. Acad. Sci. U.S.A. 90, 11713–11717 (1993).
Sun, X. J., Crimmins, D. L., Myers, M. G., Miralpeix, M. & White, M. F. Molec. cell. Biol 13, 7418–7428 (1993).
Songyang, Z. et al. Molec. cell. Biol. 14, 2777–2785 (1994).
Songyang, Z. et al. Cell 72, 767–778 (1993).
Gustafson, T. A., He, W., Craparo, A., Schaub, C. D. & O'Neill, T. J. Molec. cell. Biol. 15, 2500–2508 (1995).
Wang, J., Auger, K. R., Jarvis, L., Shi, Y. & Roberts, T. M. J. biol. Chem. 270, 12774–12780 (1995).
Myers, M. G. & White, M. F. Diabetes 42, 643–650 (1993).
Soltoff, S. P., Carraway, K.L., Prigent, S.A., Gullick, W.G. & Cantley, L.C. Molec. cell. Biol. 14, 3550–3558 (1994).
Lamphere, L., Carpenter, C. L., Sheng, Z.-F., Kallen, R. G. & Lienhard, G. E. Am. J. Physiol. 266, E486–494 (1994).
Baltensperger, K. et al. Science 260, 1950–1952 (1993).
Yamauchi, K. & Pessin, J. E. J. biol. Chem. 269, 31107–31114 (1994).
Pruett, W. et al. Molec. cell. Biol. 15, 1778–1785 (1995).
Chen, D., Van Horn, D, J., White, M. F. & Backer, J. M. Molec. cell. Biol. 15, 4711–4717 (1995).
Schlaepfer, D. D., Hanks, S. K., Hunter, T. & van der Geer, P. Nature 372, 786–791 (1994).
Vuori, K. & Ruoslahti, E. Science 266, 1576–1578 (1994).
Tamemoto, H. et al. Nature 372, 182–186 (1994).
Araki, E. et al. Nature 372, 186–190 (1994).
Sun, X. J. et al. Nature 377, 173–177 (1995).
Feng, S., Chen, J. K., Yu, H., Simon, J. A. & Schreiber, S. L. Science 266, 1241–1247 (1994).
Moscatello, D. K. et al. Cancer Res. 55, 5536–5539 (1995).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Holgado-Madruga, M., Emlet, D., Moscatello, D. et al. A Grb2-associated docking protein in EGF- and insulin-receptor signalling. Nature 379, 560–564 (1996). https://doi.org/10.1038/379560a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/379560a0
