RT Journal Article SR Electronic T1 Dual Role of Phosphatidylinositol-3,4,5-trisphosphate in the Activation of Protein Kinase B JF Science JO Science FD American Association for the Advancement of Science SP 567 OP 570 DO 10.1126/science.277.5325.567 VO 277 IS 5325 A1 Stokoe, David A1 Stephens, Leonard R. A1 Copeland, Terry A1 Gaffney, Piers R. J. A1 Reese, Colin B. A1 Painter, Gavin F. A1 Holmes, Andrew B. A1 McCormick, Frank A1 Hawkins, Phillip T. YR 1997 UL http://science.sciencemag.org/content/277/5325/567.abstract AB 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.