Hagiwara M, Mamiya S, Ochiai M, Hidaka H
Department of Molecular and Cellular Pharmacology, Mie University School of Medicine, Japan.
Biochem Biophys Res Commun. 1988 Apr 15;152(1):270-6. doi: 10.1016/s0006-291x(88)80710-1.
L-Thyroxine (T4) and L-triiodothyronine (T3) specifically, inhibited myosin light chain kinase (MLC-kinase) from various tissues whereas inhibitory effects of T4 and T3 on other protein kinases such as protein kinase C, cAMP-dependent protein kinase, casein kinase I, casein kinase II and calmodulin kinase II were much weaker. T4 was a more potent inhibitor of MLC-kinase than T3. Kinetic studies showed that T4 behaved as a competitive inhibitor of MLC-kinase toward calmodulin (CaM) and that Ki value was 2.5 microM. The activity of the catalytic fragment of MLC-kinase, which is active without CaM, was not inhibited by T4. 125I-T4 gel overlay revealed that CaM did not bind T4 but MLC-kinase had 125I-T4 binding activity. These observations suggest that T4 binds at or near CaM binding domain of MLC-kinase and inhibits CaM-induced activation of MLC-kinase.
L-甲状腺素（T4）和L-三碘甲状腺原氨酸（T3）能特异性抑制来自各种组织的肌球蛋白轻链激酶（MLC激酶），而T4和T3对其他蛋白激酶如蛋白激酶C、环磷酸腺苷依赖性蛋白激酶、酪蛋白激酶I、酪蛋白激酶II和钙调蛋白激酶II的抑制作用则弱得多。T4是比T3更有效的MLC激酶抑制剂。动力学研究表明，T4作为MLC激酶对钙调蛋白（CaM）的竞争性抑制剂，其抑制常数（Ki）值为2.5微摩尔。在没有CaM时具有活性的MLC激酶催化片段的活性不受T4抑制。125I-T4凝胶覆盖法显示CaM不结合T4，但MLC激酶具有125I-T4结合活性。这些观察结果表明，T4在MLC激酶的CaM结合结构域或其附近结合，并抑制CaM诱导的MLC激酶激活。
