Epidermoid carcinoma-derived antimicrobial peptide (ECAP) inhibits phosphorylation by protein kinases in vitro

Animal peptide antibiotics are thought to mediate their cytotoxic and growth inhibitory action on bacteria, fungi, and cancer cells through a membrane‐targeted mechanism. Although the membrane interactions of the peptide antibiotics and their penetration through the membranes have been studied in se...

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Published in:	Cell biochemistry and function Vol. 19; no. 4; pp. 291 - 298
Main Authors:	Hobta, Andriy, Lisovskiy, Igor, Mikhalap, Svitlana, Kolybo, Denis, Romanyuk, Svitlana, Soldatkina, Maria, Markeyeva, Nataliya, Garmanchouk, Liudmila, Sidorenko, Svitlana P., Pogrebnoy, Petro V.
Format:	Journal Article
Language:	English
Published:	Chichester, UK John Wiley & Sons, Ltd 01-12-2001
Subjects:	Animals Antimicrobial Cationic Peptides - isolation & purification Antimicrobial Cationic Peptides - pharmacology Carcinoma, Squamous Cell - chemistry cationic antimicrobial peptide Cell Fractionation Cell Line Cell Membrane - chemistry Cell Membrane - metabolism Chromatography, High Pressure Liquid ECAP Erythrocytes - drug effects Hemolysis - drug effects Humans peptide antibiotic Phosphorylation Precipitin Tests protein kinase inhibitor protein kinases Protein Kinases - metabolism Receptor, Epidermal Growth Factor - metabolism Tumor Cells, Cultured
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Summary:	Animal peptide antibiotics are thought to mediate their cytotoxic and growth inhibitory action on bacteria, fungi, and cancer cells through a membrane‐targeted mechanism. Although the membrane interactions of the peptide antibiotics and their penetration through the membranes have been studied in several models, the precise chain of events leading to cell death or growth arrest is not established yet. In this study we used in vitro kinase assays followed by imaging analyses to examine the effect of human cationic antimicrobial peptide ECAP on the activity of the protein kinases. We report that HPLC‐grade ECAP is responsible for inhibition of EGFR autophosphorylation in plasma membrane fractions obtained from A‐431 cells. The activity of ECAP is concentration dependent with a half‐inhibitory concentration in the range of 0.1–0.2 μM. Marked decrease in autophosphorylation of immunoprecipitated non‐receptor protein kinases belonging to different families, namely PKCμ, Lyn and Syk, is observed in the presence of as little as 0.2 μM of the peptide. Among the examined non‐receptor protein kinases PKCμ was the most sensitive to the inhibitory action of ECAP, whereas Syk was inhibited least of all. ECAP exerted no detectable cytotoxicity on non‐nucleate animal cells at concentrations up to 3 μM. The capability of ECAP to inhibit protein kinases at concentrations, that are at least 10 fold lower than antibacterial and cytotoxic ones, suggests that the protein kinases are possible intracellular targets for antimicrobial peptides. We suppose that inhibition of the protein kinases may provide a mechanism for the action of cationic antimicrobial peptides on host cells including tumour cells. Copyright © 2001 John Wiley & Sons, Ltd.
Bibliography:	State Fund for Fundamental Research - No. 5.4/388 Government of Ukraine - No. PSU084050; No. PSU084056 Howard Hughes Medical Institute - No. 75195-548101 Institute of Open Society (USA) ArticleID:CBF929 Ukrainian Council of Science - No. 2/1297-97 ark:/67375/WNG-WLTGC8F3-0 istex:7251261B4EC2285DC6D73CE4F0395442F7285E74 Please contact firstly by E‐mail due to possible change of postal address. ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0263-6484 1099-0844
DOI:	10.1002/cbf.929