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

    Science (American Association for the Advancement of Science), 07/1997, Letnik: 277, Številka: 5325
    Journal Article

    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.