Akt/Protein Kinase B Is Regulated by Autophosphorylation at the Hypothetical PDK-2 Site
作者： Alex Toker , Alexandra C. Newton
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摘要: The function of Akt (protein kinase B) is regulated by phosphorylation on two sites conserved within the AGC family: activation loop (Thr-308) in core and a hydrophobic site carboxyl terminus (Ser-473). Thr-308 phosphorylated phosphoinositide-dependent kinase-1, (PDK-1), whereas mechanism site, tentatively referred to as PDK-2 unknown. Here we report that motif requires catalytically competent Akt. First show kinase-inactive construct fails incorporate phosphate at Ser-473 following IGF-1 stimulation vivo but does second carboxyl-terminal Thr-450; this ligand triggers both wild-type enzyme. Neither inactive which blocked, T308A, become response stimulation. Second, autophosphorylates vitro: PDK-1 kinase-active, not thermally inactivated, α. Thus, autophosphorylation site.
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