Myosin Phosphatase Target Subunit 1 (MYPT1) Regulates the Contraction and Relaxation of Vascular Smooth Muscle and Maintains Blood Pressure
Myosin Phosphatase Target Subunit 1 (MYPT1) Regulates the Contraction and Relaxation of Vascular Smooth Muscle and Maintains Blood Pressure
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肌球蛋白磷酸酶靶亚基1（MYPT1）调节血管平滑肌的收缩和舒张并维持血压。
DOI：
10.1074/jbc.m113.525444
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发表时间：
2014-08-08
影响因子：
4.8
通讯作者：
Zhu, Min-Sheng
中科院分区：
文献类型：
--
作者：
Qiao, Yan-Ning;He, Wei-Qi;Zhu, Min-Sheng
肌球蛋白轻链磷酸酶及其调节亚基，肌球蛋白磷酸酶靶亚基1（MYPT 1）通过肌球蛋白轻链激酶调节肌球蛋白轻链的Ca 2+依赖性磷酸化，这是平滑肌收缩所必需的。在成年MYPT 1平滑肌特异性敲除小鼠中研究MYPT 1在血管平滑肌中的作用。MYPT 1缺失增强了KCl和各种血管激动剂处理的离体肠系膜动脉中肌球蛋白调节轻链的磷酸化和收缩力。Rho相关激酶（ROCK）和蛋白激酶C抑制剂抑制基因敲除小鼠去甲肾上腺素的动脉收缩反应，并与肌球蛋白轻链磷酸酶抑制剂CPI-17的磷酸化抑制有关。此外，NO/cGMP/蛋白激酶G（PKG）信号通路的刺激仍然导致MYPT 1缺陷的肠系膜动脉舒张，表明PKG对MYPT 1的磷酸化不是舒张反应的主要贡献者。因此，MYPT 1增强肌球蛋白轻链磷酸酶活性足以维持血压。CPI-17的Rho相关激酶磷酸化在增强血管收缩反应中起重要作用，而NO/cGMP/PKG信号传导模块中MYPT 1的磷酸化对于舒张不是必需的。
Myosin light chain phosphatase with its regulatory subunit, myosin phosphatase target subunit 1 (MYPT1) modulates Ca2+ dependent phosphorylation of myosin light chain by myosin light chain kinase, which is essential for smooth muscle contraction. The role of MYPT1 in vascular smooth muscle was investigated in adult MYPT1 smooth muscle specific knock-out mice. MYPT1 deletion enhanced phosphorylation of myosin regulatory light chain and contractile force in isolated mesenteric arteries treated with KCl and various vascular agonists. The contractile responses of arteries from knock-out mice to norepinephrine were inhibited by Rho-associated kinase (ROCK) and protein kinase C inhibitors and were associated with inhibition of phosphorylation of the myosin light chain phosphatase inhibitor CPI-17. Additionally, stimulation of the NO/cGMP/protein kinase G (PKG) signaling pathway still resulted in relaxation of MYPT1-deficient mesenteric arteries, indicating phosphorylation of MYPT1 by PKG is not a major contributor to the relaxation response. Thus, MYPT1 enhances myosin light chain phosphatase activity sufficient for blood pressure maintenance. Rho-associated kinase phosphorylation of CPI-17 plays a significant role in enhancing vascular contractile responses, whereas phosphorylation of MYPT1 in the NO/cGMP/PKG signaling module is not necessary for relaxation.