DUAL ROLE OF PHOSPHATIDYLINOSITOL-3,4,5-TRISPHOSPHATE IN THE ACTIVATION OF PROTEIN-KINASE-B

Protein kinase B (PKB) is a proto-oncogene that is activated in signal ing pathways initiated by phosphoinositide 3-kinase. Chromatographic s eparation of brain cytosol revealed a kinase activity that phosphoryla ted and activated PKB only in the presence of phosphatidylinositol-3,4 ,5-trisphosphate [PtdIns(3,4,5)P-3]. Phosphorylation occurred exclusiv ely on threonine-308, a residue implicated in activation of PKB in viv o. 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 phosphory lation by the upstream kinase and it directly activated the upstream k inase.