Yao X
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
Handb Exp Pharmacol. 2007(179):527-40. doi: 10.1007/978-3-540-34891-7_31.
Ca2+, nitric oxide (NO), and protein kinase G (PKG) are important signaling molecules that play pivotal roles in many physiological processes such as vascular tone control, platelet activation, and synaptic plasticity. TRPC channels allow Ca2+ influx, thus contributing to the production of NO, which subsequently stimulates PKG. It has been demonstrated that PKG can phosphorylate human TRPC3 at Thr-11 and Ser-263 and that this phosphorylation inactivates TRPC3. These two PKG phosphorylation sites, Thr-11 and Ser-263 in human TRPC3, are conserved in other members of the TRPC3/6/7 subfamily, suggesting that PKG may also phosphorylate TRPC6 and TRPC7. In addition, protein kinase C (PKC) also inactivates TRPC3, partly through activating PKG. The PKG-mediated inhibition of TRPC channels may provide a feedback control for the fine tuning of [Ca2+]i levels and protect the cells from the detrimental effects of excessive [Ca2+]i and/or NO.
钙离子（Ca2+）、一氧化氮（NO）和蛋白激酶G（PKG）是重要的信号分子，在许多生理过程中发挥关键作用，如血管张力控制、血小板活化和突触可塑性。瞬时受体电位经典型通道（TRPC通道）允许Ca2+内流，从而促进NO的产生，进而刺激PKG。已证实PKG可使人类TRPC3在苏氨酸-11（Thr-11）和丝氨酸-263（Ser-263）位点发生磷酸化，且这种磷酸化会使TRPC3失活。人类TRPC3中的这两个PKG磷酸化位点，即Thr-11和Ser-263，在TRPC3/6/7亚家族的其他成员中保守，这表明PKG也可能使TRPC6和TRPC7发生磷酸化。此外，蛋白激酶C（PKC）也可使TRPC3失活，部分是通过激活PKG实现的。PKG介导的对TRPC通道的抑制作用可能为细胞内钙离子浓度（[Ca2+]i）水平的微调提供反馈控制，并保护细胞免受过量[Ca2+]i和/或NO的有害影响。
