Sobieszek A
Institute of Molecular Biology, Salzburg, Austria.
Tsitologiia. 1998;40(6):568-78.
Myosin kinase and phosphatase, phosphorylating and dephosphorylating regulatory light chain of myosin, are the key regulatory enzymes of smooth muscle. They are tightly associated not only with myosin filament but also with each other and, therefore, appear to form a functional complex which is responsible for regulation of contraction and relaxation of smooth muscle. In our recent studies we have shown that the complex includes the kinase with its activator (calmodulin; CM) and the phosphatase in a form of catalytic and targeting subunits. The targeting subunit, being a CM binding protein, links the catalytic subunit to the kinase and to CM in a Ca-independent manner. In solution, the kinase is not exclusively monomeric but also dimerise and forms small amounts of oligomers, and all these forms are in equilibrium with each other. The dimers are responsible for a cooperative activation of the kinase by CM as well as for its intramolecular autophosphorylation, while the oligomeric form is involved in kinase localization on the myosin filament and also participates in formation of the complex with phosphatase. A kinase related protein (telokin) acts as a very effective modulator of the oligomeric state of the kinase by transferring the oligomers into the dimers and/or monomers. Telokin was effectively releasing the kinase from myosin filaments and the phosphatase from the complex with resulting inhibition of myosin phosphorylation and acceleration of myosin dephosphorylation. These modulating effects were reversed by a very slow phosphorylation of telokin by the kinase.
肌球蛋白激酶和磷酸酶分别使肌球蛋白的调节轻链磷酸化和去磷酸化，它们是平滑肌的关键调节酶。它们不仅与肌球蛋白丝紧密相连，而且彼此紧密相关，因此似乎形成了一个功能复合体，负责调节平滑肌的收缩和舒张。在我们最近的研究中，我们发现该复合体包括带有其激活剂（钙调蛋白；CM）的激酶以及催化亚基和靶向亚基形式的磷酸酶。靶向亚基作为一种CM结合蛋白，以不依赖钙的方式将催化亚基与激酶和CM连接起来。在溶液中，激酶不仅以单体形式存在，还会二聚化并形成少量寡聚体，所有这些形式相互处于平衡状态。二聚体负责CM对激酶的协同激活以及其分子内的自磷酸化，而寡聚体形式则参与激酶在肌球蛋白丝上的定位，并且还参与与磷酸酶形成复合体。一种激酶相关蛋白（telokin）通过将寡聚体转化为二聚体和/或单体，作为激酶寡聚状态的非常有效的调节剂。Telokin有效地使激酶从肌球蛋白丝上释放出来，并使磷酸酶从复合体中释放出来，从而抑制肌球蛋白磷酸化并加速肌球蛋白去磷酸化。激酶对telokin的非常缓慢的磷酸化作用可逆转这些调节作用。
