MYPT1 Regulates the Contraction and Relaxation of Vascular Smooth Muscle and Maintains Blood Pressure [Molecular Bases of Disease]

June 20th, 2014 by Qiao, Y.-N., He, W.-Q., Chen, C.-P., Zhang, C.-H., Zhao, W., Wang, P., Zhang, L., Wu, Y.-Z., Yang, X., Peng, Y.-J., Gao, J.-M., Kamm, K. E., Stull, J. T., Zhu, M.-S.

Myosin light chain phosphatase with its regulatory subunit MYPT1 modulates Ca2+-dependent phosphorylation of myosin light chain by myosin light chain kinase which is essential for smooth muscle contraction. The role of MYPT1 in vascular smooth muscle was investigated in adult MYPT1 smooth muscle specific knockout mice. MYPT1 deletion enhanced phosphorylation of myosin regulatory light chain and contractile force in isolated mesenteric arteries treated with KCl and various vascular agonists. The contractile responses of arteries from knockout mice to norepinephrine were inhibited by Rho-associated kinase (ROCK) and protein kinase C inhibitors and were associated with inhibition of phosphorylation of the myosin light chain phosphatase inhibitor CPI-17. Additionally, stimulation of the NO/cGMP/PKG signaling pathway still resulted in relaxation of MYPT1-deficient mesenteric arteries, indicating phosphorylation of MYPT1 by PKG is not a major contributor to the relaxation response. Thus, MYPT1 enhances myosin light chain phosphatase activity sufficient for blood pressure maintenance. ROCK phosphorylation of CPI-17 plays a significant role in enhancing vascular contractile responses while phosphorylation of MYPT1 in the NO/cGMP/PKG signaling module is not necessary for relaxation.