A tightly associated serine/threonine protein kinase regulates phosphoinositide 3-kinase activity.

作者：Christopher L. Carpenter, K R Auger, Brian C. Duckworth, Wen-Kui Hou, Brian S. Schaffhausen, Lewis C. Cantley · 发表于：Molecular and Cellular Biology · 年份：1993 · DOI：10.1128/mcb.13.3.1657 · 被引用次数：97 · 研究领域：Biochemical and Molecular Research、PI3K/AKT/mTOR signaling in cancer、Peptidase Inhibition and Analysis

We identified a serine/threonine protein kinase that is associated with and phosphorylates phosphoinositide 3-kinase (PtdIns 3-kinase). The serine kinase phosphorylates both the 85- and 110-kDa subunits of PtdIns 3-kinase and purifies with it from rat liver and immunoprecipitates with antibodies raised to the 85-kDa subunit. Tryptic phosphopeptide maps indicate that p85 from polyomavirus middle T-transformed cells is phosphorylated in vivo at three sites phosphorylated in vitro by the associated serine kinase. The 85-kDa subunit of PtdIns 3-kinase is phosphorylated in vitro on serine at a stoichiometry of approximately 1 mol of phosphate per mol of p85. This phosphorylation results in a three- to sevenfold decrease in PtdIns 3-kinase activity. Dephosphorylation with protein phosphatase 2A reverses the inhibition. This suggests that the association of protein phosphatase 2A with middle T antigen may function to activate PtdIns 3-kinase.