Silinsky Eugene M, Searl Timothy J
Department of Molecular Pharmacology and Biological Chemistry, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, U.S.A.
Br J Pharmacol. 2003 Apr;138(7):1191-201. doi: 10.1038/sj.bjp.0705213.
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.
本综述聚焦于佛波酯的作用以及佛波酯受体在神经递质物质分泌中的作用。我们首先简要介绍一下佛波酯作为工具在解析酶蛋白激酶C在信号转导级联反应中的作用方面的历史应用背景。接下来,我们阐述活性佛波酯与非活性佛波酯之间的结构差异,以及佛波醇与其在特定蛋白质上的识别位点(C1结构域)结合后促使该蛋白质转运至细胞膜的机制。然后,我们讨论如下证据:佛波酯(及其内源性对应物二酰基甘油)最重要的神经末梢受体可能是Munc13。事实上,Munc13及其无脊椎动物同源物是启动分泌装置以使其在胞吐过程中发挥关键功能的主要参与者。