Science · 1998 · 835 citations · 12 references
Life SciencesBiochemistryMolecular BiologyCell SignalingProtein TranslationSignal TransductionPhosphoinositide SignalingPost-translational RegulationProtein Kinase CascadesProtein PhosphorylationProtein SynthesisKinase Activation MechanismsMitogen-activated Protein Kinase KinaseMitogen-activated Protein Kinase PathwaysPhosphoinositide KinasesProtein Kinase B SignalingProtein Synthesis Signaling
Activation of the protein p70s6k by mitogens leads to increased translation of a family of messenger RNAs that encode essential components of the protein synthetic apparatus. Activation of the kinase requires hierarchical phosphorylation at multiple sites, culminating in the phosphorylation of the threonine in position 229 (Thr229), in the catalytic domain. The homologous site in protein kinase B (PKB), Thr308, has been shown to be phosphorylated by the phosphoinositide-dependent protein kinase PDK1. A regulatory link between p70s6k and PKB was demonstrated, as PDK1 was found to selectively phosphorylate p70s6k at Thr229. More importantly, PDK1 activated p70s6k in vitro and in vivo, whereas the catalytically inactive PDK1 blocked insulin-induced activation of p70s6k.
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Inhibition of glycogen synthase kinase-3 by insulin mediated by protein kinase B
Darren A.E. Cross, Dario R. Alessi, Philip Cohen et al. · Nature · 1995 · 5.2K citations
Dual Role of Phosphatidylinositol-3,4,5-trisphosphate in the Activation of Protein Kinase B
David Stokoe, Terry Copeland, Piers R. J. Gaffney et al. · Science · 1997 · 1.2K citations