Activated Gαq Inhibits p110α Phosphatidylinositol 3-Kinase and Akt
作者： Lisa M. Ballou , Hong-Ying Lin , Gaofeng Fan , Ya-Ping Jiang , Richard Z. Lin
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摘要: Some Gq-coupled receptors have been shown to antagonize growth factor activation of phosphatidylinositol 3-kinase (PI3K) and its downstream effector, Akt. We used a constitutively active Gαq(Q209L) mutant explore the effects Gαq on signaling through PI3K/Akt pathway. Transient expression in Rat-1 fibroblasts inhibited Akt induced by platelet-derived or insulin treatment. Expression also attenuated promoted coexpression PI3K human embryonic kidney 293 cells. had no effect activity an which two regulatory phosphorylation sites were changed acidic amino acids. Inducible stably transfected cell line caused decrease p110α (but not p110β) immunoprecipitates. Receptor selectively Active still cells pretreated with phospholipase C inhibitor U73122. Finally, co-immunoprecipitated p110α-p85α heterodimer from lysates COS-7 expressing these proteins, incubation immunoprecipitated purified recombinant vitro led activity. These results suggest that agonist binding blocks via release subunits inhibit PI3K. The inhibitory mechanism seems be independent might involve interaction between
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