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Mol Cell Biol. 1993 March; 13(3): 1657-1665

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

C L Carpenter, K R Auger, B C Duckworth, W M Hou, B Schaffhausen and L C Cantley

Hematology-Oncology Division, Beth Israel Hospital, Boston, Massachusetts.

ABSTRACT

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.

Mol Cell Biol. 1993 March; 13(3): 1657-1665




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