Protein kinase C activation by cis-fatty acid in the absence of Ca2+ and phospholipids

K. Murakami, S. Y. Chan, A. Routtenberg

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251 Scopus citations

Abstract

Protein kinase C has been shown to be a phospholipid/Ca2+-dependent enzyme activated by diacylglycerol (Nishizuka, Y. (1984) Nature 308, 693-697; Nishizuka, Y. (1984) Science 225, 1365-1370). We have reported that unsaturated fatty acids (oleic acid and arachidonic acid) can activate protein kinase C independently of Ca2+ and phospholipid (Murakami, K., and Routtenberg, A. (1985) FEBS Lett. 192, 189-193). This study shows that other cis-fatty acids such as linoleic acid also fully activate protein kinase C in the same manner. None of the saturated fatty acids (C:4 to C:18) nor the detergents (sodium dodecyl sulfate and Triton X-100) tested here were as effective as oleic acid. Unlike oleic acid, these detergents strongly inhibited protein kinase C activity induced by Ca2+/phosphatidylserine (PS) and diacylglycerol. Lowering the critical micelle concentration of oleic acid by increasing ionic strength also strongly inhibited oleic acid activation of protein kinase C activity. Dioleoylphosphatidylserine activated protein kinase C effectively (K(a) = 7.2 μM). On the other hand, dimyristoylphosphatidylserine, which contains saturated fatty acids as both acyl positions, failed to activate protein kinase C even in the presence of Ca2+. These observations suggest that: 1) protein kinase C activation by free fatty acid is specific to the cis-form and is not due to their detergent-like action, 2) cis-fatty acid activation is due to the direct interaction of protein kinase C with the monomeric form of cis-fatty acids and not with the micelles of fatty acids, and 3) cis-fatty acids at acyl positions in PS are also important for Ca2+/PS activation of protein kinase C.

Original languageEnglish (US)
Pages (from-to)15424-15429
Number of pages6
JournalJournal of Biological Chemistry
Volume261
Issue number33
StatePublished - Dec 1 1986

ASJC Scopus subject areas

  • Biochemistry

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