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Sci. Signal., 28 April 2009
Vol. 2, Issue 68, p. ra17
[DOI: 10.1126/scisignal.2000118]


Editor's Summary

Double Duty
The activation of the serine-threonine kinase Akt and of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) are important for cellular responses to growth factors, including epidermal growth factor (EGF); however, exactly how the EGF receptor (EGFR) stimulates activation of Akt is unclear. Cao et al. provide evidence of a role for the heterotrimeric guanine nucleotide–binding proteins (G proteins) G{alpha}i1 and G{alpha}i3, better known as transducers of G protein–coupled receptor signaling, in this process. Both G proteins formed complexes with EGFR and the adaptor protein Gab1 and were required for the phosphorylation of Gab1, its interaction with the p85 subunit of phosphatidylinositol 3-kinase (PI3K), and for the phosphorylation of downstream targets of Akt and mTORC1. Further, loss of both G{alpha}i1 and G{alpha}i3 impaired the migration, survival, and growth of fibroblasts in response to EGF. Together, these data suggest that these members of the G{alpha}i family of G proteins are required for EGF-mediated activation of Akt and mTORC1, providing further evidence of a role for G proteins in mediating signaling from receptor tyrosine kinases.

Citation: C. Cao, X. Huang, Y. Han, Y. Wan, L. Birnbaumer, G. S. Feng, J. Marshall, M. Jiang, W. M. Chu, G{alpha}i1 and G{alpha}i3 Are Required for Epidermal Growth Factor–Mediated Activation of the Akt-mTORC1 Pathway. Sci. Signal. 2, ra17 (2009).

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