Metastasis-associated protein Mts1 (S100A4) inhibits CK2-mediated phosphorylation and self-assembly of the heavy chain of nonmuscle myosin
Metastasis-associated protein Mts1 (S100A4) inhibits CK2-mediated phosphorylation and self-assembly of the heavy chain of nonmuscle myosin
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DOI：
10.1016/s0167-4889(00)00100-2
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发表时间：
2000-12-20
影响因子：
5.1
通讯作者：
Lukanidin, E
中科院分区：
文献类型：
--
作者：
Kriajevska, M;Bronstein, IB;Lukanidin, E
研究了EF-手型钙结合蛋白Mts 1（S100 A4）在肌球蛋白丝磷酸化和组装中的作用。非肌肉肌球蛋白分子形成双极丝，与肌动蛋白丝相互作用产生收缩力。肌球蛋白的磷酸化在肌球蛋白组装中起调节作用。在存在钙的情况下，Mts 1结合在肌球蛋白重链的C末端，靠近蛋白激酶CK 2（Ser 1944）磷酸化位点。在本研究中，我们已经表明，Mts 1与人血小板肌球蛋白或肌球蛋白重链的C-末端片段的相互作用抑制蛋白激酶CK 2在体外的肌球蛋白重链的磷酸化。Mts 1也可能直接结合蛋白激酶CK 2的β亚基，从而改变酶的活性。我们的研究结果表明，肌球蛋白低聚物被拆解的Mts 1的存在下。肌球蛋白重链的短C-末端片段在低离子条件下（50 mM NaCl）等摩尔量的Mts 1的存在下是完全可溶的。解聚被发现是钙依赖性的，可以被EGTA阻断。我们的数据表明，Mts 1可以增加肌球蛋白的溶解度，因此抑制其组装。(C)2000 Elsevier Science B. V.保留所有权利。
A role for EF-hand calcium-binding protein Mts1 (S100A4) in the phosphorylation and the assembly of myosin filaments was studied. The nonmuscle myosin molecules form bipolar filaments, which interact with actin filaments to produce a contractile force. Phosphorylation of the myosin plays a regulatory role in the myosin assembly. In the presence of calcium, Mts1 binds at the C-terminal end of the myosin heavy chain close to the site of phosphorylation by protein kinase CK2 (Ser1944). In the present study, we have shown that interaction of Mts1 with the human platelet myosin or C-terminal fragment of the myosin heavy chain inhibits phosphorylation of the myosin heavy chain by protein kinase CK2 in vitro. Mts1 might also bind directly the beta subunit of protein kinase CK2, thereby modifying the enzyme activity. Our results indicate that myosin oligomers were disassembled in the presence of Mts1. The short C-terminal fragment of the myosin heavy chain was totally soluble in the presence of an equimolar amount of Mts1 at low ionic conditions (50 mM NaCl). Depolymerization was found to be calcium-dependent and could be blocked by EGTA. Our data suggest that Mts1 can increase myosin solubility and therefore suppress its assembly. (C) 2000 Elsevier Science B.V. All rights reserved.