Department of Pharmaceutical Sciences, Bouvé College of Health Sciences and College of Science, Northeastern University, Boston, Massachusetts, USA.
Department of Pharmaceutical Sciences, Bouvé College of Health Sciences and College of Science, Northeastern University, Boston, Massachusetts, USA; Department of Chemistry and Chemical Biology, Bouvé College of Health Sciences and College of Science, Northeastern University, Boston, Massachusetts, USA; Center for Drug Discovery, Bouvé College of Health Sciences and College of Science, Northeastern University, Boston, Massachusetts, USA.
J Biol Chem. 2022 Jun;298(6):102035. doi: 10.1016/j.jbc.2022.102035. Epub 2022 May 16.
Ion channels are integral membrane proteins whose gating has been increasingly shown to depend on the presence of the low-abundance membrane phospholipid, phosphatidylinositol (4,5) bisphosphate. The expression and function of ion channels is tightly regulated via protein phosphorylation by specific kinases, including various PKC isoforms. Several channels have further been shown to be regulated by PKC through altered surface expression, probability of channel opening, shifts in voltage dependence of their activation, or changes in inactivation or desensitization. In this review, we survey the impact of phosphorylation of various ion channels by PKC isoforms and examine the dependence of phosphorylated ion channels on phosphatidylinositol (4,5) bisphosphate as a mechanistic endpoint to control channel gating.
离子通道是整合膜蛋白,其门控越来越多地被证明依赖于低丰度膜磷脂,即磷脂酰肌醇(4,5)双磷酸的存在。离子通道的表达和功能通过特定激酶的蛋白质磷酸化进行严格调节,包括各种蛋白激酶 C(PKC)同工型。进一步研究表明,几种通道通过 PKC 调节通过改变表面表达、通道开放的概率、它们的激活的电压依赖性的改变、或失活或脱敏的改变来进行调节。在这篇综述中,我们调查了 PKC 同工型对各种离子通道的磷酸化的影响,并检查了磷酸化离子通道对磷脂酰肌醇(4,5)双磷酸的依赖性,作为控制通道门控的机制终点。