期刊
BIOCHEMICAL JOURNAL
卷 441, 期 -, 页码 189-198出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20111318
关键词
cofactor; oxidation; protein kinase C alpha; alpha-tocopherol; gamma-tocopherol; vitamin E
资金
- National Institutes of Health [R01 AT004837, GM68849]
Vitamin E isoforms have opposing regulatory effects on leucocyte recruitment during inflammation. Furthermore, in vitro, vitamin E isoforms have opposing effects on leucocyte migration across endothelial cells by regulating VCAM (vascular cell-adhesion molecule)-1 activation of endothelial cell PKC alpha (protein kinase C alpha). However, it is not known whether tocopherols directly regulate cofactor-dependent or oxidative activation of PKC alpha. We report in the present paper that cofactor-dependent activation of recombinant PKC alpha was increased by gamma-tocopherol and was inhibited by alpha-tocopherol. Oxidative activation of PKC alpha was inhibited by alpha-tocopherol at a 10-fold lower concentration than gamma-tocopherol. In binding studies, NBD (7-nitrobenz-2-oxa-1,3-diazole)-tagged alpha-tocopherol directly bound to full-length PKC alpha or the PKC alpha-C1a domain, but not PKC zeta. NBD-tagged alpha-tocopherol binding to PKC alpha or the PKC alpha-C1a domain was blocked by diacylglycerol, alpha-tocopherol, gamma-tocopherol and retinol, but not by cholesterol or PS (phosphatidylserine). Tocopherols enhanced PKC alpha-C2 domain binding to PS-containing lipid vesicles. In contrast, the PKC alpha-C2 domain did not bind to lipid vesicles containing tocopherol without PS. The PKC alpha-C1b domain did not bind to vesicles containing tocopherol and PS. In summary, alpha-tocopherol and gamma-tocopherol bind the diacylglycerol-binding site on PKC alpha-C1a and can enhance PKC alpha-C2 binding to PS-containing vesicles. Thus the tocopherols can function as agonists or antagonists for differential regulation of PKC alpha.
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