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.
Nakabayashi
H
H
Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
Brown
J H
JH
Morell
J L
JL
Chen
H C
HC
Huang
K P
KP
D000595:Amino Acid Sequence; D000818:Animals; D000890:Anti-Infective Agents / Q000378:metabolism* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D055598:Chemical Phenomena; D002621:Chemistry; D007527:Isoenzymes / Q000378:metabolism / Q000502:physiology*; D054806:Magainins; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D029867:Xenopus Proteins; D014982:Xenopus laevis
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D007527:Isoenzymes; D054806:Magainins; D010455:Peptides; D029867:Xenopus Proteins; C053301:magainin 2 peptide, Xenopus; D011493:Protein Kinase C