Dual role of phosphatidylinositol-3, 4, 5-trisphosphate in the activation of protein kinase B

D Stokoe, LR Stephens, T Copeland, PRJ Gaffney… - Science, 1997 - science.org
D Stokoe, LR Stephens, T Copeland, PRJ Gaffney, CB Reese, GF Painter, AB Holmes…
Science, 1997science.org
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 …
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.
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