Department of Physiology, University of Texas Southwestern Medical Center, Dallas, 75390-9040, USA.
Arch Biochem Biophys. 2011 Jun 15;510(2):120-8. doi: 10.1016/j.abb.2011.01.017. Epub 2011 Feb 1.
Skeletal muscle myosin light chain kinase (skMLCK) is a dedicated Ca(2+)/calmodulin-dependent serine-threonine protein kinase that phosphorylates the regulatory light chain (RLC) of sarcomeric myosin. It is expressed from the MYLK2 gene specifically in skeletal muscle fibers with most abundance in fast contracting muscles. Biochemically, activation occurs with Ca(2+) binding to calmodulin forming a (Ca(2+))(4)•calmodulin complex sufficient for activation with a diffusion limited, stoichiometric binding and displacement of a regulatory segment from skMLCK catalytic core. The N-terminal sequence of RLC then extends through the exposed catalytic cleft for Ser15 phosphorylation. Removal of Ca(2+) results in the slow dissociation of calmodulin and inactivation of skMLCK. Combined biochemical properties provide unique features for the physiological responsiveness of RLC phosphorylation, including (1) rapid activation of MLCK by Ca(2+)/calmodulin, (2) limiting kinase activity so phosphorylation is slower than contraction, (3) slow MLCK inactivation after relaxation and (4) much greater kinase activity relative to myosin light chain phosphatase (MLCP). SkMLCK phosphorylation of myosin RLC modulates mechanical aspects of vertebrate skeletal muscle function. In permeabilized skeletal muscle fibers, phosphorylation-mediated alterations in myosin structure increase the rate of force-generation by myosin cross bridges to increase Ca(2+)-sensitivity of the contractile apparatus. Stimulation-induced increases in RLC phosphorylation in intact muscle produces isometric and concentric force potentiation to enhance dynamic aspects of muscle work and power in unfatigued or fatigued muscle. Moreover, RLC phosphorylation-mediated enhancements may interact with neural strategies for human skeletal muscle activation to ameliorate either central or peripheral aspects of fatigue.
骨骼肌肌球蛋白轻链激酶（skMLCK）是一种专门的 Ca2+/钙调蛋白依赖性丝氨酸/苏氨酸蛋白激酶，可磷酸化肌球蛋白的调节轻链（RLC）。它由 MYLK2 基因特异性表达，主要存在于快收缩肌肉的骨骼肌纤维中。从生物化学角度来看，当 Ca2+与钙调蛋白结合形成足以激活的（Ca2+）4·钙调蛋白复合物时，skMLCK 就会发生激活，该复合物通过扩散限制、化学计量结合和将调节片段从 skMLCK 催化核心置换出来，从而实现激活。然后，RLC 的 N 端序列通过暴露的催化裂缝延伸，以便 Ser15 磷酸化。Ca2+的去除导致钙调蛋白的缓慢解离和 skMLCK 的失活。综合生化特性为 RLC 磷酸化的生理反应提供了独特的特征，包括（1）Ca2+/钙调蛋白快速激活 MLCK，（2）限制激酶活性，从而使磷酸化比收缩慢，（3）松弛后 MLCK 缓慢失活，以及（4）与肌球蛋白轻链磷酸酶（MLCP）相比，激酶活性更高。skMLCK 对肌球蛋白 RLC 的磷酸化调节了脊椎动物骨骼肌功能的力学方面。在通透的骨骼肌纤维中，磷酸化介导的肌球蛋白结构变化增加了肌球蛋白横桥的力生成速率，从而增加了收缩装置的 Ca2+敏感性。在完整肌肉中，刺激诱导的 RLC 磷酸化增加会产生等长和向心力量增强，从而增强肌肉工作和未疲劳或疲劳肌肉的功率的动力方面。此外，RLC 磷酸化介导的增强可能与人类骨骼肌激活的神经策略相互作用，以改善疲劳的中枢或外周方面。
