title: Dual role of phosphatidylinositol-3,4,5-trisphosphate in the activation of protein kinase B.
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.
authors.affiliation: Onyx Pharmaceuticals, 3031 Research Drive, Richmond, CA 94806, USA. stokoe@cc.ucsf.edu
authors.forename: D
authors.initials: D
authors.lastname: Stokoe
authors.forename: L R
authors.initials: LR
authors.lastname: Stephens
authors.forename: T
authors.initials: T
authors.lastname: Copeland
authors.forename: P R
authors.initials: PR
authors.lastname: Gaffney
authors.forename: C B
authors.initials: CB
authors.lastname: Reese
authors.forename: G F
authors.initials: GF
authors.lastname: Painter
authors.forename: A B
authors.initials: AB
authors.lastname: Holmes
authors.forename: F
authors.initials: F
authors.lastname: McCormick
authors.forename: P T
authors.initials: PT
authors.lastname: Hawkins
mesh_terms: D064413:3-Phosphoinositide-Dependent Protein Kinases; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001798:Blood Proteins / Q000737:chemistry; D001921:Brain / Q000201:enzymology; D019556:COS Cells; D003600:Cytosol / Q000201:enzymology; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D010750:Phosphoproteins; D010766:Phosphorylation; D010769:Phosphothreonine / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013237:Stereoisomerism
chemical_list: D001798:Blood Proteins; C000715470:MAS1 protein, human; D018129:Phosphatidylinositol Phosphates; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; C060974:phosphatidylinositol 3,4,5-triphosphate; C039077:platelet protein P47; D010769:Phosphothreonine; D000255:Adenosine Triphosphate; D064413:3-Phosphoinositide-Dependent Protein Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt