Myosin phosphatase: Structure, regulation and function
Myosin phosphatase: Structure, regulation and function
复制标题
DOI：
10.1023/b:mcbi.0000021373.14288.00
复制
发表时间：
2004-04-01
影响因子：
4.3
通讯作者：
Hartshorne, DJ
中科院分区：
文献类型：
--
作者：
Ito, M;Nakano, T;Hartshorne, DJ
肌球蛋白II的磷酸化在许多细胞功能中起重要作用，包括平滑肌收缩。肌球蛋白II磷酸化水平由肌球蛋白轻链激酶和肌球蛋白磷酸酶（MP）的活性决定。MP由3个亚基组成：1型磷酸酶的催化亚基，PP 1c;靶向亚基，称为肌球蛋白磷酸酶靶亚基，MYPT;和较小的亚基，M20，功能未知。MP的大部分性质是由于MYPT，包括PP 1c和底物的结合。讨论了其他相互作用。最近的发现是MYPT家族的存在，其成员包括MYPT 1、MYPT 2、MBS 85、MYPT 3和TIMAP。每个人的特点进行了概述。一个重要的发现是MP的活性可以被调节，并且有激活和抑制的报道。激活反应于升高的环核苷酸水平而发生，并提出了各种机制。MP的抑制是平滑肌中Ca 2+敏化的主要组成部分，并讨论了各种分子机制。两种机制经常被引用：（1）MYPT 1，Thr 696（人类同种型）上抑制位点的磷酸化和PP 1c活性的抑制。几种激酶可以磷酸化Thr 696，包括在平滑肌功能中起重要作用的Rho-激酶;和（2）通过17 kDa的蛋白激酶C增强的抑制剂蛋白（CPI-17）抑制MP。这些机制涉及平滑肌功能的例子。RhoA/Rho激酶信号在各种系统中的关键作用进行了讨论，特别是那些血管平滑肌疾病涉及hypercontractility。
Phosphorylation of myosin II plays an important role in many cell functions, including smooth muscle contraction. The level of myosin II phosphorylation is determined by activities of myosin light chain kinase and myosin phosphatase ( MP). MP is composed of 3 subunits: a catalytic subunit of type 1 phosphatase, PP1c; a targeting subunit, termed myosin phosphatase target subunit, MYPT; and a smaller subunit, M20, of unknown function. Most of the properties of MP are due to MYPT and include binding of PP1c and substrate. Other interactions are discussed. A recent discovery is the existence of an MYPT family and members include, MYPT1, MYPT2, MBS85, MYPT3 and TIMAP. Characteristics of each are outlined. An important discovery was that the activity of MP could be regulated and both activation and inhibition were reported. Activation occurs in response to elevated cyclic nucleotide levels and various mechanisms are presented. Inhibition of MP is a major component of Ca2+-sensitization in smooth muscle and various molecular mechanisms are discussed. Two mechanisms are cited frequently: (1) Phosphorylation of an inhibitory site on MYPT1, Thr696 ( human isoform) and resulting inhibition of PP1c activity. Several kinases can phosphorylate Thr696, including Rho-kinase that serves an important role in smooth muscle function; and ( 2) Inhibition of MP by the protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17). Examples where these mechanisms are implicated in smooth muscle function are presented. The critical role of RhoA/Rho-kinase signaling in various systems is discussed, in particular those vascular smooth muscle disorders involving hypercontractility.