Regulation of myosin phosphorylation and myofilament Ca2+ sensitivity in vascular smooth muscle

Katsuya Hirano, Mayumi Hirano, Hideo Kanaide

研究成果: Contribution to journalReview article査読

62 被引用数 (Scopus)

抄録

The Ca2+-dependent, reversible phosphorylation of the 20 kDa regulatory myosin light chain (MLC) plays a primary role in regulating the contraction of smooth muscle. However, it is well known that the Ca2+ signal is not the only factor which regulates such contraction, however, the alteration of the Ca2+ sensitivity in the contractile apparatus is also known to play an important role. The degree of MLC phosphorylation is determined by the balance of the activity between phosphorylation and dephosphorylation. Either the Ca2+-independent activation of MLC phosphorylation or the inhibition of MLC dephosphorylation causes a greater MLC phosphorylation for a given level of Ca2+ signal and thereby potentiates the myofilament Ca2+ sensitivity. The smooth muscle myosin light chain phosphatase (MLCP) consisting of three subunits was first isolated and cloned in the early '90s. The intensive investigation thereafter has uncovered the biochemical basis for regulating the activity of MLCP. The regulation of the MLCP activity is now considered to play a critical role in regulating the myofilament Ca2+ sensitivity. There are three major mechanisms in the regulation of MLCP; (1) the phosphorylation of a 110 kDa regulatory subunit of MLCP (2) the conformational change of the trimeric structure, and (3) the inhibition by a smooth muscle specific inhibitor protein, CPI-17. Furthermore, some kinases have been found to phosphorylate the MLC and activate the contraction of smooth muscle in a Ca2+-independent manner. Numerous protein kinases have been found to be involved in the regulation of MLC phosphorylation, and rho-kinase is one of the most frequently investigated kinases. The smooth muscle physiology is now asked to integrate the current understanding of the biochemical mechanisms and to clarify which kinases and/or proteins in the contractile apparatus play a physiological role in regulating the myofilament Ca2+ sensitivity and how such extracellular contractile stimulation modulates these mechanisms.

本文言語英語
ページ(範囲)219-236
ページ数18
ジャーナルJournal of Smooth Muscle Research
40
6
DOI
出版ステータス出版済み - 12 2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • Physiology

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