Research ArticleG Proteins

i1 and Gαi3 Are Required for Epidermal Growth Factor–Mediated Activation of the Akt-mTORC1 Pathway

Science Signaling  28 Apr 2009:
Vol. 2, Issue 68, pp. ra17
DOI: 10.1126/scisignal.2000118

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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) Gαi1 and Gαi3, 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 Gαi1 and Gαi3 impaired the migration, survival, and growth of fibroblasts in response to EGF. Together, these data suggest that these members of the Gαi 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.