Phosphorylation of magainin-2 by protein kinase C and inhibition of protein kinase C isozymes by a synthetic analogue of magainin-2-amide.

Magainins are a family of antimicrobial peptides present in the skin extracts of Xenopus laevis. Both magainin-1 and -2 do not have any significant effect on the activity of protein kinase C (PKC). Magainin-2 was found to be readily phosphorylated by PKC to 0.5 mol 32P/mol of peptide. Neither magainin-1, which has a sequence of S8AGK and not S8AKK as in the case of magainin-2, nor the magainin-2 analogue with substitution of Ala for Ser8 was phosphorylated by the kinase, suggesting that Ser8 is the phosphorylation site of magainin-2. One synthetic analogue of magainin, designated magainin B, which has a greater tendency for alpha-helix formation in non-aqueous environment than the parent peptide resulting from substitution of Ser8, Gly13, and Gly18 with Ala in magainin-2-amide, is a potent inhibitor of PKC. This peptide inhibits all three PKC isozymes with IC50 less than 20 microM. Magainin B also inhibits the binding of [3H]phorbol 12,13-dibutyrate to the kinase. These results suggest that magainin-2 may be modified by PKC through phosphorylation and that certain synthetic analogues of magainins may be used as inhibitors of PKC.