Insulin-activated protein kinases phosphorylate a pseudosubstrate synthetic peptide inhibitor of the p70 S6 kinase.
p70 S6 kinase, a major insulin-mitogen-activated ribosomal S6 protein kinase in mammalian cells, is activated by phosphorylation of multiple Ser/Thr residues on the enzyme polypeptide. A synthetic peptide, corresponding to a 37-residue segment from the carboxyl-terminal tail of the kinase which resembles the sequence phosphorylated in S6, acts as a competitive inhibitor of p70 S6 kinase without itself being phosphorylated by the enzyme. This synthetic peptide is phosphorylated by an array of protein kinases which are rapidly activated by insulin. Thus, these sequences of p70 S6 kinase constitute a potential autoinhibitory pseudosubstrate site, whose phosphorylation is catalyzed by candidate upstream-activating protein kinases.
Price
D J
DJ
Diabetes Unit, Massachusetts General Hospital, Boston 02129.
Mukhopadhyay
N K
NK
Avruch
J
J
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D004789:Enzyme Activation; D007328:Insulin / Q000502:physiology*; D008114:Liver Neoplasms, Experimental; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D019893:Ribosomal Protein S6 Kinases; D012694:Serine / Q000378:metabolism; D013379:Substrate Specificity; D013970:Thyronines / Q000378:metabolism; D014407:Tumor Cells, Cultured
D007328:Insulin; D010455:Peptides; D047428:Protein Kinase Inhibitors; D013970:Thyronines; D012694:Serine; D011494:Protein Kinases; D019893:Ribosomal Protein S6 Kinases