Protein kinase C contains a pseudosubstrate prototope in its regulatory domain.
The regulatory domain of protein kinase C contains an amino acid sequence between residues 19 and 36 that resembles a substrate phosphorylation site in its distribution of basic residue recognition determinants. The corresponding synthetic peptide (Arg19-Phe-Ala-Arg-Lys-Gly-Ala25-Leu-Arg-Gln-Lys-Asn-Val-His -Glu-Val-Lys-Asn36) acts as a potent substrate antagonist with an inhibitory constant of 147 +/- 9 nM. It is a specific inhibitor of protein kinase C and inhibits both autophosphorylation and protein substrate phosphorylation. Substitution of Ala25 with serine transforms the pseudosubstrate into a potent substrate. These results demonstrate that the conserved region of the regulatory domain (residues 19 to 36) of protein kinase C has the secondary structural features of a pseudosubstrate and may be responsible for maintaining the enzyme in the inactive form in the absence of allosteric activators such as phospholipids.
Department of Medicine, University of Melbourne, Repatriation General Hospital, West Heidelberg, Victoria, Australia.
C
C
House
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Kemp
D000595:Amino Acid Sequence; D000818:Animals; D006706:Homeostasis; D007700:Kinetics; D009219:Myosin-Light-Chain Kinase / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D013379:Substrate Specificity
D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase