Dual Role of Phosphatidylinositol-3,4,5-trisphosphate in the Activation of Protein Kinase B

David Stokoe; Leonard R. Stephens; Terry Copeland; Piers R. J. Gaffney; Colin B. Reese; Gavin F. Painter; Andrew B. Holmes; Frank McCormick; Phillip T. Hawkins

doi:10.1126/science.277.5325.567

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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.

↵* Present address: University of California, San Francisco Cancer Research Institute, 2340 Sutter Street, San Francisco, CA 94115, USA.
↵† To whom correspondence should be addressed. E-mail: stokoe{at}cc.ucsf.edu

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Dual Role of Phosphatidylinositol-3,4,5-trisphosphate in the Activation of Protein Kinase B

Abstract

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