Galpha(i1) and Galpha(i3) are required for epidermal growth factor-mediated activation of the Akt-mTORC1 pathway.

ABSTRACT: The precise mechanism whereby epidermal growth factor (EGF) activates the serine-threonine kinase Akt and the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) remains elusive. Here, we report that the alpha subunits of the heterotrimeric guanine nucleotide-binding proteins (G proteins) Galpha(i1) and Galpha(i3) are critical for this activation process. Both Galpha(i1) and Galpha(i3) formed complexes with growth factor receptor binding 2 (Grb2)-associated binding protein 1 (Gab1) and the EGF receptor (EGFR) and were required for the phosphorylation of Gab1 and its subsequent interaction with the p85 subunit of phosphatidylinositol 3-kinase in response to EGF. Loss of Galpha(i1) and Galpha(i3) severely impaired the activation of Akt and of p70 S6 kinase and 4E-BP1, downstream targets

SUBMITTER: Cao C 

PROVIDER: S-EPMC4138699 | biostudies-literature | 2009 Apr

REPOSITORIES: biostudies-literature