Specific role for p85/p110β in GTP-binding-protein-mediated activation of Akt
- 6 December 2005
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 392 (3) , 607-614
- https://doi.org/10.1042/bj20050671
Abstract
We prepared CHO (Chinese hamster ovary) cells expressing both IR (insulin receptor) and A1R (A1 adenosine receptor). Treatment of the cells with insulin or PIA [N6-(2-phenylisopropyl)adenosine], a specific A(1)R agonist increased Akt activity in the cells in a PI3K- (phosphoinositide 3-kinase) dependent manner. Transfection of p110beta into the cells augmented the action of PIA with little effect on insulin. Introduction of a pH1 vector producing shRNA (short hairpin RNA) that targets p110beta abolished PIA-induced Akt activation. By contrast, an shRNA probe targeting p110alpha did not impair the effects of PIA. The effect of PIA in p110alpha-deficient cells was attenuated effectively by both Deltap85 and betaARK-CT (beta-adrenergic receptor kinase-C-terminal peptide). A Deltap85-derived protein possessing point mutations in its two SH2 domains did not impair PIA action. These results suggest that tyrosine-phosphorylated proteins and Gbetagamma (betagamma subunits of GTP-binding protein) are necessary for the specific function of p110beta in intact cells. The p110beta-middle (middle part of p110beta) may play an important role in signal reception from GPCRs (GTP-binding-protein-coupled receptor), because transfection of the middle part impaired PIA sensitivity.Keywords
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