RT Journal Article
SR Electronic
T1 Direct Regulation of the <em>Akt</em> Proto-Oncogene Product by Phosphatidylinositol-3,4-bisphosphate
JF Science
JO Science
FD American Association for the Advancement of Science
SP 665
OP 668
DO 10.1126/science.275.5300.665
VO 275
IS 5300
A1 Franke, Thomas F.
A1 Kaplan, David R.
A1 Cantley, Lewis C.
A1 Toker, Alex
YR 1997
UL http://science.sciencemag.org/content/275/5300/665.abstract
AB The regulation of the serine-threonine kinase Akt by lipid products of phosphoinositide 3-kinase (PI 3-kinase) was investigated. Akt activity was found to correlate with the amount of phosphatidylinositol-3,4-bisphosphate (PtdIns-3,4-P2) in vivo, and synthetic PtdIns-3,4-P2 activated Akt both in vitro and in vivo. Binding of PtdIns-3,4-P2 occurred within the Akt pleckstrin homology (PH) domain and facilitated dimerization of Akt. Akt mutated in the PH domain was not activated by PI 3-kinase in vivo or by PtdIns-3,4-P2 in vitro, and it was impaired in binding to PtdIns-3,4-P2. Examination of the binding to other phosphoinositides revealed that they bound to the Akt PH domain with much lower affinity than did PtdIns-3,4-P2 and failed to increase Akt activity. Thus, Akt is apparently regulated by the direct interaction of PtdIns-3,4-P2 with the Akt PH domain.