Myosin phosphatase inactivation by ROCK

The activity of nonmuscle myosin II (NMM2) is suppressed by dephosphorylation of myosin regulatory light chains (MRLC), MYL9 and MYL12B, by the MLC phosphatase. The MLC phosphatase is composed of a catalytic subunit (PPP1CB) and two regulatory subunits, myosin phosphatase-targeting subunit 1 (MYPT1, PPP1R12A) and M20 (MYPT2, PPP1R12B). MYPT1 binds directly to myosin II. Myosin phosphatase is inhibited by ROCKs. ROCKs phosphorylate MYPT1 subunit of the myosin phosphatase at two inhibitory sites, Thr696 and Ser852, resulting in a decrease in MRLC phosphatase activity and an increase in phosphorylated MRLC (Kimura et al. 1996, Nakai et al. 1997, Katoh et al. 2001, Iwasaki et al. 2001), which promotes binding to filamentous actin and stress fibre formation. This effect is synergistic with the direct phosphorylation of MRLC by ROCKs.

非肌肉肌球蛋白II（NMM2）的活性通过肌球蛋白调节轻链（MRLC）、MYL9和MYL12B的去磷酸化受到肌动蛋白轻链磷酸酶的抑制。该磷酸酶由一个催化亚基（PPP1CB）和两个调节亚基组成，即肌球蛋白磷酸酶靶向亚基1（MYPT1，PPP1R12A）和M20（MYPT2，PPP1R12B）。MYPT1直接与肌球蛋白II结合。肌球蛋白磷酸酶受到Rho激酶（ROCKs）的抑制。ROCKs在肌球蛋白磷酸酶的MYPT1亚基的两个抑制位点Thr696和Ser852处发生磷酸化，从而降低MRLC磷酸酶活性并增加磷酸化MRLC（Kimura等，1996年，Nakai等，1997年，Katoh等，2001年，Iwasaki等，2001年），这促进了其与细丝状肌动蛋白的结合和应力纤维的形成。此效应与ROCKs直接磷酸化MRLC的作用协同。