Structure and regulation of phospholipase Cβ and ε at the membrane.

Structure and regulation of phospholipase Cβ and ε at the membrane.
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DOI:
10.1016/j.chemphyslip.2021.105050
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发表时间:
2021-03
影响因子:
3.4
通讯作者:
Lyon AM
Lyon AM
中科院分区:
生物学3区
文献类型:
--
作者:
Muralidharan K;Van Camp MM;Lyon AM

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磷脂酶C(PLC)β和ε酶水解磷脂酰肌醇(PI)脂质,以响应与异源三聚体G蛋白亚基和G蛋白偶联受体(GPCR)和受体酪氨酸激酶(RTK)下游激活的小GTP酶的直接相互作用。PI水解产生第二信使,其增加细胞内Ca2+浓度并激活蛋白激酶C(PKC),从而调节许多生理过程。PLCβ和PLCε共享脂肪酶活性所需的高度保守的核心,但使用不同的策略和结构元件来自动抑制基础活性,结合膜,并接合G蛋白激活剂。在这篇综述中,我们讨论了最近的结构见解,这些酶的影响,他们如何从事膜单独或复杂的G蛋白调节。
Phospholipase C (PLC) β and ε enzymes hydrolyze phosphatidylinositol (PI) lipids in response to direct interactions with heterotrimeric G protein subunits and small GTPases activated downstream of G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs). PI hydrolysis generates second messengers that increase the intracellular Ca2+ concentration and activate protein kinase C (PKC), thereby regulating numerous physiological processes. PLCβ and PLCε share a highly conserved core required for lipase activity but use different strategies and structural elements to autoinhibit basal activity, bind membranes, and engage G protein activators. In this review, we discuss recent structural insights into these enzymes and the implications for how they engage membranes alone or in complex with their G protein regulators.
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