title: Myosin phosphatase target subunit 1 (MYPT1) regulates the contraction and relaxation of vascular smooth muscle and maintains blood pressure.
abstract: Myosin light chain phosphatase with its regulatory subunit, myosin phosphatase target subunit 1 (MYPT1) modulates Ca(2+)-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 knock-out 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 knock-out 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/protein kinase G (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. Rho-associated kinase phosphorylation of CPI-17 plays a significant role in enhancing vascular contractile responses, whereas phosphorylation of MYPT1 in the NO/cGMP/PKG signaling module is not necessary for relaxation.
authors.affiliation: From the Key Laboratory of MOE for Modern Teaching Technology, Shaanxi Normal University, Xi'an 710062, China, Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease, Nanjing University, Nanjing 210061, China.
authors.forename: Yan-Ning
authors.initials: YN
authors.lastname: Qiao
authors.affiliation: Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease, Nanjing University, Nanjing 210061, China.
authors.forename: Wei-Qi
authors.initials: WQ
authors.lastname: He
authors.affiliation: Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease, Nanjing University, Nanjing 210061, China.
authors.forename: Cai-Ping
authors.initials: CP
authors.lastname: Chen
authors.affiliation: Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease, Nanjing University, Nanjing 210061, China.
authors.forename: Cheng-Hai
authors.initials: CH
authors.lastname: Zhang
authors.affiliation: Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease, Nanjing University, Nanjing 210061, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease, Nanjing University, Nanjing 210061, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Wang
authors.affiliation: Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: From the Key Laboratory of MOE for Modern Teaching Technology, Shaanxi Normal University, Xi'an 710062, China.
authors.forename: Yan-Ze
authors.initials: YZ
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Proteomics, Genetic Laboratory of Development and Disease, Institute of Biotechnology, Beijing 100071, China, and.
authors.forename: Xiao
authors.initials: X
authors.lastname: Yang
authors.affiliation: Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease, Nanjing University, Nanjing 210061, China.
authors.forename: Ya-Jing
authors.initials: YJ
authors.lastname: Peng
authors.affiliation: Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, China.
authors.forename: Ji-Min
authors.initials: JM
authors.lastname: Gao
authors.affiliation: the Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9040.
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Kamm
authors.affiliation: the Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas 75390-9040.
authors.forename: James T
authors.initials: JT
authors.lastname: Stull
authors.affiliation: Model Animal Research Center and MOE Key Laboratory of Animal Models of Disease, Nanjing University, Nanjing 210061, China, Zhejiang Provincial Key Laboratory for Technology and Application of Model Organisms, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, China, zhums@nju.edu.cn.
authors.forename: Min-Sheng
authors.initials: MS
authors.lastname: Zhu
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D005260:Female; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008638:Mesenteric Arteries / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D018994:Myosin Light Chains / Q000378:metabolism; D009219:Myosin-Light-Chain Kinase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D043263:Myosin-Light-Chain Phosphatase; D009569:Nitric Oxide / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D018994:Myosin Light Chains; D010750:Phosphoproteins; C491520:Ppp1r14a protein, mouse; D009569:Nitric Oxide; D009219:Myosin-Light-Chain Kinase; D043263:Myosin-Light-Chain Phosphatase; C510645:Ppp1r12a protein, mouse
keywords: Contractile Protein; Myosin; Myosin Light Chain Phosphatase, Myosin Phosphorylation, Vascular Smooth Muscle; Phosphatase; Smooth Muscle; Vascular Biology