Department of Pharmacology, Molecular Biophysics Graduate Program and Green Center for Systems Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Annu Rev Physiol. 2013;75:127-54. doi: 10.1146/annurev-physiol-030212-183750. Epub 2012 Nov 5.
Phospholipase C (PLC) converts phosphatidylinositol 4,5-bisphosphate (PIP(2)) to inositol 1,4,5-trisphosphate (IP(3)) and diacylglycerol (DAG). DAG and IP(3) each control diverse cellular processes and are also substrates for synthesis of other important signaling molecules. PLC is thus central to many important interlocking regulatory networks. Mammals express six families of PLCs, each with both unique and overlapping controls over expression and subcellular distribution. Each PLC also responds acutely to its own spectrum of activators that includes heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca(2+), and phospholipids. Mammalian PLCs are autoinhibited by a region in the catalytic TIM barrel domain that is the target of much of their acute regulation. In combination, the PLCs act as a signaling nexus that integrates numerous signaling inputs, critically governs PIP(2) levels, and regulates production of important second messengers to determine cell behavior over the millisecond to hour timescale.
磷脂酶 C（PLC）将磷脂酰肌醇 4,5-二磷酸（PIP(2)）转化为肌醇 1,4,5-三磷酸（IP(3)）和二酰基甘油（DAG）。DAG 和 IP(3) 各自控制着不同的细胞过程，也是合成其他重要信号分子的底物。因此，PLC 是许多重要的连锁调节网络的核心。哺乳动物表达六种 PLC 家族，每个家族都对表达和亚细胞分布有独特和重叠的控制。每种 PLC 还对其自身的一系列激活剂做出急性反应，其中包括异三聚体 G 蛋白亚基、蛋白酪氨酸激酶、小 G 蛋白、Ca(2+)和磷脂。哺乳动物 PLC 被其催化 TIM 桶结构域中的一个区域自动抑制，该区域是其急性调节的主要靶点。综合来看，PLC 作为一个信号枢纽，整合了众多信号输入，对 PIP(2) 水平的调控至关重要，并调节重要第二信使的产生，以在毫秒到小时的时间尺度上决定细胞行为。
