期刊
BIOCHEMICAL JOURNAL
卷 452, 期 -, 页码 195-209出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20130220
关键词
kinase activator; kinase inhibitor; kinase reporter; phorbol ester; protein kinase C (PKC)
资金
- National Institutes of Health [GM43154, P01 DK054441]
- University of California, San Diego Graduate Training Program in Cellular and Molecular Pharmacology through the National Institute of General Medical Sciences [T32 GM007752]
PKC (protein kinase C) has been in the limelight since the discovery three decades ago that it acts as a major receptor for the tumour-promoting phorbol esters. Phorbol esters, with their potent ability to activate two of the three classes of PKC isoenzymes, have remained the best pharmacological tool for directly modulating PKC activity. However, with the discovery of other phorbol ester-responsive proteins, the advent of various small-molecule and peptide modulators, and the need to distinguish isoenzyme-specific activity, the pharmacology of PKC has become increasingly complex. Not surprisingly, many of the compounds originally touted as direct modulators of PKC have subsequently been shown to hit many other cellular targets and, in some cases, not even directly modulate PKC. The complexities and reversals in PKC pharmacology have led to widespread confusion about the current status of the pharmacological tools available to control PKC activity. In the present review, we aim to clarify the cacophony in the literature regarding the current state of bona fide and discredited cellular PKC modulators, including activators, small-molecule inhibitors and peptides, and also address the use of genetically encoded reporters and of PKC mutants to measure the effects of these drugs on the spatiotemporal dynamics of signalling by specific isoenzymes.
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