Smooth Muscle Research Group and Department of Biochemistry and Molecular Biology, University of Calgary, Calgary, Alberta T2N 4N1, Canada.
IUBMB Life. 2011 Nov;63(11):987-1000. doi: 10.1002/iub.527. Epub 2011 Oct 12.
Smooth muscle contraction is activated primarily by phosphorylation at S19 of the 20-kDa regulatory light chain subunits of myosin II (LC(20) ) catalyzed by Ca(2+) /calmodulin-dependent myosin light chain kinase. Other kinases, for example, integrin-linked kinase (ILK), Rho-associated kinase (ROCK), and zipper-interacting protein kinase (ZIPK), can phosphorylate T18 in addition to S19, which increases the actin-activated myosin MgATPase activity at subsaturating actin concentrations ∼3-fold. These phosphorylatable residues and the amino acid sequence surrounding them are highly conserved throughout the animal kingdom; they are also found in an LC(20) homolog within the genome of Monosiga brevicollis, the closest living relative of metazoans. LC(20) diphosphorylation has been detected in mammalian vascular smooth muscle tissues in response to specific contractile stimuli and in pathophysiological situations associated with hypercontractility. LC(20) diphosphorylation has also been observed frequently in cultured cells where it activates force generation. Kinases such as ILK, ROCK, and ZIPK, therefore, are potential therapeutic targets in the treatment of, for example, cerebral vasospasm following subarachnoid hemorrhage and atherosclerosis.
平滑肌收缩主要通过肌球蛋白 II（肌球蛋白 II）的 20kDa 调节轻链亚基 S19 的磷酸化激活，该磷酸化由 Ca(2+) /钙调蛋白依赖性肌球蛋白轻链激酶催化。其他激酶，例如整合素连接激酶（ILK）、Rho 相关激酶（ROCK）和拉链相互作用蛋白激酶（ZIPK），除了 S19 之外还可以磷酸化 T18，这会增加肌球蛋白 MgATP 酶在亚饱和肌动蛋白浓度下的活性约 3 倍。这些可磷酸化的残基及其周围的氨基酸序列在整个动物界高度保守；它们也存在于后生动物最接近的近亲 Monosiga brevicollis 的基因组中的 LC(20) 同源物中。LC(20) 双磷酸化已在哺乳动物血管平滑肌组织中检测到，以响应特定的收缩刺激和与高收缩性相关的病理生理情况。LC(20) 双磷酸化也经常在培养细胞中观察到，在培养细胞中它会激活力的产生。因此，ILK、ROCK 和 ZIPK 等激酶是治疗蛛网膜下腔出血后脑血管痉挛和动脉粥样硬化等疾病的潜在治疗靶点。
