Regulation of Protein Kinase Cμ by Basic Peptides and Heparin

Autor: Franz-Josef Johannes, Friedrich Marks, Walter Kittstein, Michael Gschwendt
Rok vydání: 1997
Předmět:
Zdroj: Journal of Biological Chemistry. 272:20742-20746
ISSN: 0021-9258
DOI: 10.1074/jbc.272.33.20742
Popis: Protein kinase Cμ is a novel member of the protein kinase C (PKC) family that differs from the other isoenzymes in structural and enzymatic properties. No substrate proteins of PKCμ have been identified as yet. Moreover, the regulation of PKCμ activity remains obscure, since a structural region corresponding to the pseudosubstrate domains of other PKC isoenzymes has not been found for PKCμ. Here we show that aldolase is phosphorylated by PKCμ in vitro. Phosphorylation of aldolase and of two substrate peptides by PKCμ is inhibited by various proteins and peptides, including typical PKC substrates such as histone H1, myelin basic protein, and p53. This inhibitory activity seems to depend on clusters of basic amino acids in the protein/peptide structures. Moreover, in contrast to other PKC isoenzymes PKCμ is activated by heparin and dextran sulfate. Maximal activation by heparin is about twice and that by dextran sulfate four times as effective as maximal activation by phosphatidylserine plus 12-O-tetradecanoylphorbol-13-acetate, the conventional activators of c- and nPKC isoforms. We postulate that PKCμ contains an acidic domain, which is involved in the formation and stabilization of an active state and which, in the inactive enzyme, is blocked by an intramolecular interaction with a basic domain. This intramolecular block is thought to be released by heparin and possibly also by 12-O-tetradecanoylphorbol-13-acetate/phosphatidylserine, whereas basic peptides and proteins inhibit PKCμ activity by binding to the acidic domain of the active enzyme.
Databáze: OpenAIRE