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.
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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
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DOI: https://doi.org/10.1038/379560a0
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