Dual Role of Phosphatidylinositol-3,4,5-trisphosphate in the Activation of Protein Kinase B
David Stokoe(Babraham Institute), Leonard R. Stephens(Babraham Institute), Terry Copeland(Babraham Institute), Piers R. J. Gaffney(Babraham Institute), Colin B. Reese(Babraham Institute), Gavin F. Painter(Babraham Institute), Andrew B. Holmes(Babraham Institute), Frank McCormick(Babraham Institute), Phillip T. Hawkins(Babraham Institute)
Cited by 1,209
Abstract
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.
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