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Phorbol esters and neurotransmitter release: more than just protein kinase C?
Author(s) -
Silinsky Eugene M,
Searl Timothy J
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705213
Subject(s) - protein kinase c , diacylglycerol kinase , prkcq , phorbol , microbiology and biotechnology , biochemistry , exocytosis , signal transduction , receptor , protein kinase a , neurotransmitter , neurotransmitter receptor , biology , chemistry , secretion , kinase , phorbol ester
This review focuses on the effects of phorbol esters and the role of phorbol ester receptors in the secretion of neurotransmitter substances. We begin with a brief background on the historical use of phorbol esters as tools to decipher the role of the enzyme protein kinase C in signal transduction cascades. Next, we illustrate the structural differences between active and inactive phorbol esters and the mechanism by which the binding of phorbol to its recognition sites (C1 domains) on a particular protein acts to translocate that protein to the membrane. We then discuss the evidence that the most important nerve terminal receptor for phorbol esters (and their endogenous counterpart diacylglycerol) is likely to be Munc13. Indeed, Munc13 and its invertebrate homologues are the main players in priming the secretory apparatus for its critical function in the exocytosis process. British Journal of Pharmacology (2003) 138 , 1191–1201. doi: 10.1038/sj.bjp.0705213