Phosphorylation and Activation of p70 s6k by PDK1

• DOI: 10.1126/science.279.5351.707
• Publication Date: 2002-07-27T09:37:46Z
• Authors: Nicholas Pullen; Patrick B. Dennis; Mirjana Andjelkovic; Almut Dufner; Sara C. Kozma; Brian A. Hemmings; George Thomas
• Keywords: 0303 health sciences; Binding Sites; Molecular Sequence Data; Polyenes; Protein Serine-Threonine Kinases; Catalysis; Recombinant Proteins; Cell Line; 3-Phosphoinositide-Dependent Protein Kinases; Androstadienes; Enzyme Activation; Insulin Antagonists; 03 medical and health sciences; Phosphothreonine; Proto-Oncogene Proteins; Calcium-Calmodulin-Dependent Protein Kinases; Animals; Insulin; Amino Acid Sequence; Phosphorylation; Proto-Oncogene Proteins c-akt; Calcium-Calmodulin-Dependent Protein Kinase Type 4

Activation of the protein p70 s6k 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 (Thr 229 ), in the catalytic domain. The homologous site in protein kinase B (PKB), Thr 308 , has been shown to be phosphorylated by the phosphoinositide-dependent protein kinase PDK1. A regulatory link between p70 s6k and PKB was demonstrated, as PDK1 was found to selectively phosphorylate p70 s6k at Thr 229 . More importantly, PDK1 activated p70 s6k in vitro and in vivo, whereas the catalytically inactive PDK1 blocked insulin-induced activation of p70 s6k .