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局部磷脂酰肌醇-4,5-二磷酸(PIP(2))信号:何时、何地以及如何产生?

Local PIP(2) signals: when, where, and how?

作者信息

Hilgemann Donald W

机构信息

Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, 75390-9040, USA.

出版信息

Pflugers Arch. 2007 Oct;455(1):55-67. doi: 10.1007/s00424-007-0280-9. Epub 2007 May 30.

Abstract

PIP(2) is a minor phospholipid that modulates multiple cellular processes. However, its abundance by mass, like diacylglycerol, is still 20 to 100 times greater than the master phospholipid second messenger, PIP(3). Therefore, it is a case-by-case question whether PIP(2) is acting more like GTP, in being a cofactor in regulatory processes, or whether it is being used as a true second messenger. Analysis of signaling mechanisms in primary cells is essential to answer this question, as overexpression studies will naturally generate false positives. In connection with the possible messenger function of PIP(2), a second question arises as to how and if PIP(2) metabolism and signaling may be limited in space. This review summarizes succinctly the notable cases in which PIP(2) is proposed to function in a localized way and the different mechanistic models that may allow it to function locally. In general, drastic restrictions of PIP(2) diffusion are required. It is speculated that molecular PIP(2) signaling may be possible in the absence of PIP(2) gradients via ternary complexes between PIP(2) and two protein partners. That PIP(2) synthesis and hydrolysis might be locally dependent on protein-protein interactions, and direct lipid "hand-off" is suggested by multiple results.

摘要

磷脂酰肌醇-4,5-二磷酸(PIP(2))是一种调节多种细胞过程的次要磷脂。然而,与二酰基甘油一样,按质量计算其丰度仍比主要的磷脂第二信使磷脂酰肌醇-3,4,5-三磷酸(PIP(3))大20至100倍。因此,PIP(2)在调节过程中作为辅助因子时,其作用是否更类似于鸟苷三磷酸(GTP),或者它是否被用作真正的第二信使,这是一个因情况而异的问题。分析原代细胞中的信号传导机制对于回答这个问题至关重要,因为过表达研究自然会产生假阳性结果。关于PIP(2)可能的信使功能,第二个问题是PIP(2)代谢和信号传导如何以及是否可能在空间上受到限制。本综述简要总结了PIP(2)被认为以局部方式发挥作用的显著案例,以及可能使其在局部发挥作用的不同机制模型。一般来说,需要对PIP(2)的扩散进行严格限制。据推测,在没有PIP(2)梯度的情况下,通过PIP(2)与两个蛋白质伙伴之间的三元复合物,分子PIP(2)信号传导可能是可行的。多项研究结果表明,PIP(2)的合成和水解可能局部依赖于蛋白质-蛋白质相互作用以及直接的脂质“传递”。

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