Protein Kinase B Kinases That Mediate Phosphatidylinositol 3,4,5-Trisphosphate-Dependent Activation of Protein Kinase B
作者： Len Stephens , Karen Anderson , David Stokoe , Hediye Erdjument-Bromage , Gavin F. Painter
DOI: 10.1126/SCIENCE.279.5351.710
关键词: Biochemistry 、 Phosphatidylinositol (3,4,5)-trisphosphate 、 Phosphatidylinositol 、 Signal transduction 、 Pleckstrin homology domain 、 Protein kinase A 、 Protein kinase B 、 Kinase 、 AKT1 、 Biology 、 Multidisciplinary
摘要: Protein kinase B (PKB) is activated in response to phosphoinositide 3-kinases and their lipid products phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] PtdIns(3,4)P2in the signaling pathways used by a wide variety of growth factors, antigens, inflammatory stimuli. PKB direct target these lipids, but this regulation complex. The lipids can bind pleckstrin homologous domain PKB, causing its translocation membrane, also enable upstream, Thr308-directed kinases phosphorylate activate PKB. Four isoforms were purified from sheep brain. They bound PtdIns(3,4,5)P3and associated with vesicles containing it. These contain an NH2-terminal catalytic COOH-terminal domain, heterologous expression augments receptor activation which suggests they are primary signal transducers that PtdIns(3,4,5)P3 or PtdIns- (3,4)P2 hence control regulating cell survival, glucose uptake, glycogen metabolism.
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