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.