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

FEBS Letters

Nakabayashi, Hiroki¹  Huang, Kuo-Ping¹  Chen, Hao-Chia¹  Morell, John L.¹  Brown, Judith H.¹ 

[1] Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA

关键词: Protein kinase C;    Inhibitor;    Magainin;    Phosphorylation;    PKC;    protein kinase C;    PKM;    the catalytic fragment of PKC;    PS;    phosphatidylserine;    DOG;    dioleoylglycerol;    PDBu;    phorbol 12;    13-dibutyrate;    NP-40;    Nonidet P-40;   

DOI  :  10.1016/0014-5793(90)80307-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 α-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 μM. 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.

【 授权许可】

Unknown