The Function and Abnormality of myosin phosphatase in cardiovascular system

本文对肌球蛋白磷酸酶在心血管系统中的功能和异常进行了较为详细的研究，并获得了以下结果：1.平滑肌中肌球蛋白磷酸酶（myosin phosphnatase，MP）的信号转导机制：Rho激酶在体外磷酸化MP的调节亚基（myosin phosphnatase，MYPT），使MP的全酶失活。在Triton-X-100透性化的兔门静脉平滑肌中，组成性活性Rho激酶可引起收缩。这种收缩伴随着单磷酸化肌球蛋白轻链的成比例增加。以上结果表明，MP和Rho激酶是调节平滑肌张力的重要因子。2.两种人MYPT亚型的鉴定我们在人中鉴定了两种新的MP MYPT亚型。MYPT 1同种型与大鼠或鸡同种型非常相似，并且显示>80%的序列同一性。MYPT 1主要定位于各种平滑肌组织中。MYPT 1基因定位于12号染色体（12 q15-q21.2）。MYPT 2基因定位于1号染色体（1q32.1）上，主要分布于心脏和脑组织。最近的研究表明，染色体1q32.1含有心肌病的致病基因。因此，我们认为MYPT 2可能与心肌病的发生有关。关于这一点，还需要进一步的研究。3. MP与磷脂的相互作用研究了MP与膜组分，即各种磷脂的相互作用。发现MYPT的C-末端部分与酸性磷脂相互作用。进一步表明MYPT被PKA磷酸化，MP全酶的磷酸化降低了磷脂结合，磷酸酶活性恢复。这些结果支持MP可能与膜相互作用的想法，PKA的磷酸化可以改变这种相互作用。

The function and abnormality of myosin phosphatase in cardiovascular system has been characterized in some detail and the following results have been presented.1.Signal transduction mechanism through myosin phospnatase (MP) in smooth muscle Rho-kinase phosphorylated the regulatory subunit (MYPT) of MP and inactivated the holoenzyme in vitro. Constitutively active Rho-kinase can induce contraction in Triton-X-100-permeabilized smooth muscle of rabbit portal vein. This contraction was accompanied by proportional increases in monophosphorylated myosin light chain. From above results it seems that MP and Rho-kinase are the important factors responsible for the regulation of smooth muscle tone.2.Identification of two human MYPT isoformsWe have identified two novel isoforms of MYPT of MP in human. MYPT1 isoform is quite similar to rat or chicken isoforms and show>80% sequence identity. MYPT1 is mainly located in various smooth muscle tissues. The gene of MYPT1 was found on chromosome 12 (12q15-q21.2). On the other hand, MYPT2 is found in heart and brain.and its gene was localized on chromosome 1 (1q32.1). Recent study shows that chromosome 1q32.1 contains the putative genes responsible for cardiomyopathy. Therefore we suggest that MYPT2 may be related to the occurrence of cardiomyopathy. With regard to this, further studies will be needed.3.Interaction of MP and phospholipidsThe interaction of MP with membrane components, i.e.various phospholipids was examined. The C-terminal part of MYPT was found to interact the acidic phospholipids. It was further shown that MYPT was phosphorylated by PKA and that phosphorylation of the MP holoenzyme decreased phospholipid binding with a recovery of phosphatase activity. These results support the idea that MP may interact with membranes and that phosphorylation by PKA could modify this interaction.