title: Distinct structural requirements of Ca2+/phospholipid-dependent protein kinase (protein kinase C) and cAMP-dependent protein kinase as evidenced by synthetic peptide substrates.
abstract: Protein kinase C, purified to near homogeneity from the brain, has been tested toward a variety of synthetic peptide substrates including different phosphorylatable residues. While it proved totally inactive toward the tyrosyl peptide Asp-Ala-Glu-Tyr-Ala-Ala-Arg-Arg-Arg-Gly, as well as toward several more or less acidic seryl peptides, it phosphorylates with a Ca2+/phospholipid-dependent mechanism, at seryl and/or threonyl residues, many basic peptides, some of which are also good substrates for cAMP-dependent protein kinase (A-kinase). Among the peptides tested, however, the best substrate for protein kinase C, with kinetic constants comparable to those of histones, is the nonapeptide Gly-Ser-Arg6-Tyr, which is not a substrate for A-kinase. Moreover, although the peptide Pro-Arg5-Ser-Ser-Arg-Pro-Val-Arg is a good substrate for both kinases, its derivative with ornitines replacing arginines is phosphorylated only by protein kinase C. Some typical substrates of A-kinase on the other hand, like the peptides Phe-Arg2-Leu-Ser-Ile-Ser-Thr-Glu-Ser and Arg2-Ala-Ser-Val-Ala, are phosphorylated by protein kinase C rather slowly and with unfavourable kinetic constants. It is concluded that, while both protein kinase C and A-kinase need basic groups close to the phosphorylatable residues, their primary structure determinants are quite distinct.
authors.forename: S
authors.initials: S
authors.lastname: Ferrari
authors.forename: F
authors.initials: F
authors.lastname: Marchiori
authors.forename: G
authors.initials: G
authors.lastname: Borin
authors.forename: L A
authors.initials: LA
authors.lastname: Pinna
mesh_terms: D000818:Animals; D002417:Cattle; D007700:Kinetics; D010455:Peptides; D010766:Phosphorylation; D011493:Protein Kinase C; D011494:Protein Kinases / Q000032:analysis*; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D011494:Protein Kinases; D011493:Protein Kinase C