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.
House
C
C
Department of Medicine, University of Melbourne, Repatriation General Hospital, West Heidelberg, Victoria, Australia.
Kemp
B E
BE
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