The Function and Abnormality of myosin phosphatase in cardiovascular system

对肌球蛋白磷酸酶在心血管系统中的作用和异常进行了较为详细的研究，主要结果如下：1.肌球蛋白磷酸酶(MP)在体外通过肌球蛋白磷酸酶(MP)磷酸化调节亚基(MYPT)的信号转导机制，使其失活。结构性活性Rho-K可诱导Triton-X-100通透性的兔门静脉平滑肌收缩。这种收缩伴随着单磷酸化肌球蛋白轻链的比例增加。以上结果表明，MP和Rho-Kinase是调节肌张力的重要因素。2.两种人类MYPT亚型的鉴定我们在人类中发现了MP的两种新的MYPT亚型。MYPT1亚型与大鼠或鸡的亚型非常相似，并显示80%的序列同源性。MYPT1主要分布在多种平滑肌组织中。MYPT1基因位于12号染色体(12q15-q21.2)。另一方面，在心脏和脑中发现了MYPT2，其基因定位于1号染色体(1q32.1)。最近的研究表明，染色体1q32.1包含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。3.MP与磷脂的相互作用研究了MP与膜成分，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。进一步证明MYPT被PKA磷酸化，MP全酶的磷酸化减少了磷脂结合，恢复了磷酸酶活性。这些结果支持MP可能与膜相互作用的观点，并且PKA的磷酸化可能改变这种相互作用。

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.