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Publication : RalGDS couples growth factor signaling to Akt activation.

First Author  Hao Y Year  2008
Journal  Mol Cell Biol Volume  28
Issue  9 Pages  2851-9
PubMed ID  18285454 Mgi Jnum  J:135677
Mgi Id  MGI:3794256 Doi  10.1128/MCB.01917-07
Citation  Hao Y, et al. (2008) RalGDS couples growth factor signaling to Akt activation. Mol Cell Biol 28(9):2851-9
abstractText  The Akt kinase is a key regulator of cell proliferation and survival. It is activated in part by PDK1-induced phosphorylation. Here we show that RalGDS, a Ras effector protein that activates Ral GTPases, has a second function that promotes Akt phosphorylation by PDK1 by bringing these two kinases together. In support of this conclusion is our finding that suppression of RalGDS expression in cells inhibits both epidermal growth factor and insulin-induced phosphorylation of Akt. Moreover, while PDK1 complexes with N-GDS, Akt complexes with the central region of RalGDS through an intermediary, JIP1. The biological significance of this newly discovered RalGDS function is highlighted by the observation that an N-terminally deleted mutant of RalGDS that retains the ability to activate Ral proteins but loses the ability to activate Akt also fails to promote cell proliferation. Thus, RalGDS forms a nexus that transduces growth factor signaling to both Ral GTPase and Akt-mediated signaling cascades.
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