Characterization and function of MYPT2, a target subunit of myosin phosphatase in heart
Characterization and function of MYPT2, a target subunit of myosin phosphatase in heart
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DOI：
10.1016/j.cellsig.2005.11.001
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发表时间：
2006-09-01
影响因子：
4.8
通讯作者：
Ito, Masaaki
中科院分区：
文献类型：
--
作者：
Okamoto, Ryuji;Kato, Takaaki;Ito, Masaaki
描述了心肌MYPT 2（平滑肌磷酸酶[MP]靶亚基MYPT 1的同种型）的特征。MYPT 2和MYPT 1的几个特征相似，包括：与1型磷酸酶催化亚基的特异性相互作用，（PP 1c δ）; MYPT 2与小的心脏特异性MP亚基的相互作用; MYPT 2的C-末端区域与RhoA的活性形式的相互作用; Rho激酶在抑制位点Thr 646的磷酸化和Thr 646的硫代磷酸化抑制MYPT 2-PP 1c δ复合物的活性。MY PT 2使用平滑肌和心肌的轻链，通过降低K-m和增加k（cat）激活PP 1c δ活性。活化程度（k（cat））大于MYPT 1，可以反映两种MYPT亚型中不同的N-末端序列。腺病毒介导的MYPT 2和PP 1c delta基因转移降低了A23187刺激后心脏轻链的磷酸化水平。MYPT 2和PP 1c δ的过表达阻断了血管紧张素II诱导的心肌细胞肌节组织化。电镜观察显示MYPT位于或靠近Z线、A带和线粒体。两种MYPT亚型的相似性表明共同的酶机制和调节。心肌肌球蛋白是MYPT 2全酶的底物，但Z线位置提高了其他底物的可能性。(c)2005年爱思唯尔公司All rights reserved.
Characterization of cardiac MYPT2 (an isoform of the smooth muscle phosphatase [MP] target subunit, MYPT1) is described. Several features of MYPT2 and MYPT1 were similar, including: a specific interaction with the catalytic subunit of type 1 phosphatase, delta isoform (PP1c delta); interaction of MYPT2 with the small heart-specific MP subunit; interaction of the C-terminal region of MYPT2 with the active form of RhoA; phosphorylation by Rho-kinase at an inhibitory site, Thr646 and thiophosphorylation at Thr646 inhibited activity of the MYPT2-PP1c delta complex. MY PT2 activated PP1c delta activity, using light chains from smooth and cardiac muscle, by reducing K-m and increasing k(cat). The extent of activation (k(cat)) was greater than for MYPT1 and could reflect distinct N-terminal sequences in the two MYPT isoforms. Adenovirus-mediated gene transfer of MYPT2 and PP1c delta reduced the phosphorylation level of cardiac light chains following stimulation with A23187. Overexpression of MYPT2 and PP1c delta blocked the angiotensin II-induced sarcomere organization in cultured cardiomyocytes. Electron microscopy indicated locations of MYPTs, at, or close to, the Z-Iine, the A band and mitochondria. Similarity of the two MYPT isoforms suggests common enzymatic mechanisms and regulation. Cardiac myosin is a substrate for the MYPT2 holoenzyme, but the Z-Iine location raises the possibility of other substrates. (c) 2005 Elsevier Inc. All rights reserved.