Shears Stephen B, Ganapathi Sindura B, Gokhale Nikhil A, Schenk Tobias M H, Wang Huanchen, Weaver Jeremy D, Zaremba Angelika, Zhou Yixing
Inositol Signaling Section, Laboratory of Signal Transduction, NIEHS, NIH, DHHS, Research Triangle Park, 27709, NC, USA, USA,
Subcell Biochem. 2012;59:389-412. doi: 10.1007/978-94-007-3015-1_13.
Ins(1,4,5)P(3) is a classical intracellular messenger: stimulus-dependent changes in its levels elicits biological effects through its release of intracellular Ca(2+) stores. The Ins(1,4,5)P(3) response is "switched off" by its metabolism to a range of additional inositol phosphates. These metabolites have themselves come to be collectively described as a signaling "family". The validity of that latter definition is critically examined in this review. That is, we assess the strength of the hypothesis that Ins(1,4,5)P(3) metabolites are themselves "classical" signals. Put another way, what is the evidence that the biological function of a particular inositol phosphate depends upon stimulus dependent changes in its levels? In this assessment, examples of an inositol phosphate acting as a cofactor (i.e. its function is not stimulus-dependent) do not satisfy our signaling criteria. We conclude that Ins(3,4,5,6)P(4) is, to date, the only Ins(1,4,5)P(3) metabolite that has been validated to act as a second messenger.
肌醇-1,4,5-三磷酸（Ins(1,4,5)P(3)）是一种经典的细胞内信使：其水平的刺激依赖性变化通过释放细胞内钙库引发生物学效应。Ins(1,4,5)P(3)反应通过其代谢为一系列其他肌醇磷酸而“关闭”。这些代谢产物本身已被统称为一个信号“家族”。本综述对后一定义的有效性进行了严格审查。也就是说，我们评估了Ins(1,4,5)P(3)代谢产物本身是“经典”信号这一假设的可信度。换句话说，有什么证据表明特定肌醇磷酸的生物学功能取决于其水平的刺激依赖性变化？在这种评估中，肌醇磷酸作为辅助因子起作用的例子（即其功能不依赖于刺激）不符合我们的信号标准。我们得出结论，迄今为止，肌醇-3,4,5,6-四磷酸（Ins(3,4,5,6)P(4)）是唯一已被证实可作为第二信使发挥作用的Ins(1,4,5)P(3)代谢产物。
