DOI: 10.1126/science.277.5325.567 ISSN:
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- Multidisciplinary
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)P 3 ]. Phosphorylation occurred exclusively on threonine-308, a residue implicated in activation of PKB in vivo. PtdIns(3,4,5)P 3 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.