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描述，并报道了以下结果：平滑肌rho激酶中肌球蛋白磷酸酶（myosin phospnatase， MP）的信号转导机制使MP的调控亚基（regulatory subunit， MYPT）磷酸化并使全酶失活。组成型活性rho激酶可诱导兔门静脉triton - x -100渗透性平滑肌收缩。这种收缩伴随着单磷酸化肌球蛋白轻链成比例的增加。从以上结果来看，MP和rho激酶是平滑肌张力调节的重要因子。两种人MYPT异构体的鉴定我们鉴定了两种新的人MP的MYPT异构体。MYPT1亚型与大鼠或鸡亚型非常相似，序列同源性为80%。MYPT1主要分布在各种平滑肌组织中。MYPT1基因位于12号染色体上（12q15-q21.2）。另一方面，MYPT2存在于心脏和大脑中。其基因定位在1号染色体上（1q32.1）。最近的研究表明，染色体1q32.1含有可能导致心肌病的基因。因此，我们认为MYPT2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。MP与磷脂的相互作用考察了MP与膜组分（即各种磷脂）的相互作用。发现MYPT的c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，恢复了磷酸酶的活性。这些结果支持了MP可能与细胞膜相互作用的观点，而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.