Regulation of Phosphoinositide 3-Kinase by Its Intrinsic Serine Kinase Activity In Vivo

Abstract

One potentially important mechanism for regulating class Ia phosphoinositide 3-kinase (PI 3-kinase) activity is autophosphorylation of the p85α adapter subunit on Ser608 by the intrinsic protein kinase activity of the p110 catalytic subunit, as this downregulates the lipid kinase activity in vitro. Here we investigate whether this phosphorylation can occur in vivo. We find that p110α phosphorylates p85α Ser608 in vivo with significant stoichiometry. However, p110β is far less efficient at phosphorylating p85α Ser608, identifying a potential difference in the mechanisms by which these two isoforms are regulated. The p85α Ser608 phosphorylation was increased by treatment with insulin, platelet..