Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B.

Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B.

Science (New York, N.Y.) (1997-07-25)

D Stokoe, L R Stephens, T Copeland, P R Gaffney, C B Reese, G F Painter, A B Holmes, F McCormick, P T Hawkins

RÉSUMÉ

Protein kinase B (PKB) is a proto-oncogene that is activated in signaling pathways initiated by phosphoinositide 3-kinase. Chromatographic separation of brain cytosol revealed a kinase activity that phosphorylated and activated PKB only in the presence of phosphatidylinositol-3,4,5-trisphosphate [PtdIns(3,4,5)P3]. Phosphorylation occurred exclusively on threonine-308, a residue implicated in activation of PKB in vivo. PtdIns(3,4,5)P3 was determined to have a dual role: Its binding to the pleckstrin homology domain of PKB was required to allow phosphorylation by the upstream kinase and it directly activated the upstream kinase.