A synthetic peptide analog of the putative substrate‐binding motif activates protein kinase C

Abstract

A 29-residue synthetic peptide, Leu⁵³⁰-Leu-Tyr-Glu-Met-Leu-Ala-Gly-Gln-Ala-Pro-Phe-Glu-Gly-Glu-Asp-Glu-Asp-Glu-Leu-Phe-Gln-Ser-Ile-Met-Glu-His-Asn-Val-NH₂, ⁵⁵⁸, corresponding to part of the catalytic domain of protein kinase C, is a potent activator of the enzyme, with a K _a, of approx. 10 μM. Activation was 59 ± 4% of that observed with phosphatidylserine, predominantly due to an increased V _max, partially calcium-dependent, observed with all three isoenzymes (α, β, γ), and resulted in autophosphorylation. It is proposed that the region between Gly⁵²⁸ and Arg⁵⁸³ is part of the protein substrate binding region of protein kinase C and synthetic peptide analogs of this region activate the enzyme by blocking the action of the enzyme's basic pseudosubstrate autoregulatory region.