Sci. Signal., 28 April 2009
Double DutyThe 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) Gi1 and Gi3, 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 Gi1 and Gi3 impaired the migration, survival, and growth of fibroblasts in response to EGF. Together, these data suggest that these members of the Gi 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, Gi1 and Gi3 Are Required for Epidermal Growth Factor–Mediated Activation of the Akt-mTORC1 Pathway. Sci. Signal. 2, ra17 (2009).
The editors suggest the following Related Resources on Science sites:
In Science Signaling
In Science Magazine
Related Web Sites
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882