scholarly journals Heart-specific Small Subunit of Myosin Light Chain Phosphatase Activates Rho-associated Kinase and Regulates Phosphorylation of Myosin Phosphatase Target Subunit 1

2010 ◽  
Vol 285 (44) ◽  
pp. 33680-33690 ◽  
Author(s):  
Daisuke Shichi ◽  
Takuro Arimura ◽  
Taisuke Ishikawa ◽  
Akinori Kimura
Keyword(s):  
Light Chain ◽  
Myosin Light Chain ◽  
Small Subunit ◽  
Myosin Phosphatase ◽  
Myosin Light Chain Phosphatase

scholarly journals Recombinant Small Subunit of Smooth Muscle Myosin Light Chain Phosphatase

2001 ◽  
Vol 276 (36) ◽  
pp. 34318-34322 ◽  
Author(s):  
Knut Langsetmo ◽  
Walter F. Stafford ◽  
Katsuhide Mabuchi ◽  
Terence Tao
Keyword(s):  
Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Small Subunit ◽  
Smooth Muscle Myosin ◽  
Myosin Light Chain Phosphatase ◽  
Muscle Myosin

scholarly journals Overexpression of heart-specific small subunit of myosin light chain phosphatase results in heart failure and conduction disturbance

2018 ◽  
Vol 314 (6) ◽  
pp. H1192-H1202 ◽  
Author(s):  
Takuro Arimura ◽  
Antoine Muchir ◽  
Masayoshi Kuwahara ◽  
Sachio Morimoto ◽  
Taisuke Ishikawa ◽  
...  
Keyword(s):  
Heart Failure ◽  
Transgenic Mice ◽  
Muscle Contraction ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Small Subunit ◽  
Conduction Disturbance ◽  
Myosin Light Chain Phosphatase ◽  
Myosin Light Chain 2

Mutations in genes encoding components of the sarcomere cause cardiomyopathy, which is often associated with abnormal Ca2+ sensitivity of muscle contraction. We have previously shown that a heart-specific myosin light chain phosphatase small subunit (hHS-M21) increases the Ca2+ sensitivity of muscle contraction. The aim of the present study was to investigate the function of hHS-M21 in vivo and the causative role of abnormal Ca2+ sensitivity in cardiomyopathy. We generated transgenic mice with cardiac-specific overexpression of hHS-M21. We confirmed that hHS-M21 increased the Ca2+ sensitivity of cardiac muscle contraction in vivo, which was not followed by an increased phosphorylation of myosin light chain 2 isoforms. hHS-M21 transgenic mice developed severe systolic dysfunction with myocardial fibrosis and degeneration of cardiomyocytes in association with sinus bradycardia and atrioventricular conduction defect. The contractile dysfunction and cardiac fibrosis were improved by treatment with the Rho kinase inhibitor fasudil. Our findings suggested that the overexpression of hHS-M21 results in cardiac dysfunction and conduction disturbance via non-myosin light chain 2 phosphorylation-dependent regulation. NEW & NOTEWORTHY The present study is the first to develop mice with transgenic overexpression of a heart-specific myosin light chain phosphatase small subunit (hHS-M21) and to examine the effects of hHS-M21 on cardiac function. Elevation of hHS-M21 induced heart failure with myocardial fibrosis and degeneration of cardiomyocytes accompanied by supraventricular arrhythmias.

scholarly journals Identification, Characterization, and Functional Analysis of Heart-specific Myosin Light Chain Phosphatase Small Subunit

2000 ◽  
Vol 276 (9) ◽  
pp. 6073-6082 ◽  
Author(s):  
Takuro Arimura ◽  
Nobuhiro Suematsu ◽  
Ying-Bi Zhou ◽  
Junji Nishimura ◽  
Shinji Satoh ◽  
...  
Keyword(s):  
Functional Analysis ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Small Subunit ◽  
Myosin Light Chain Phosphatase

scholarly journals Unfair competition governs the interaction of pCPI-17 with myosin phosphatase (PP1-MYPT1)

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Joshua J Filter ◽  
Byron C Williams ◽  
Masumi Eto ◽  
David Shalloway ◽  
Michael L Goldberg
Keyword(s):  
Light Chain ◽  
Active Site ◽  
Slow Rate ◽  
Myosin Light Chain ◽  
Muscle Relaxation ◽  
Smooth Muscles ◽  
Unfair Competition ◽  
Myosin Phosphatase ◽  
Myosin Light Chain Phosphatase

The small phosphoprotein pCPI-17 inhibits myosin light-chain phosphatase (MLCP). Current models postulate that during muscle relaxation, phosphatases other than MLCP dephosphorylate and inactivate pCPI-17 to restore MLCP activity. We show here that such hypotheses are insufficient to account for the observed rapidity of pCPI-17 inactivation in mammalian smooth muscles. Instead, MLCP itself is the critical enzyme for pCPI-17 dephosphorylation. We call the mutual sequestration mechanism through which pCPI-17 and MLCP interact inhibition by unfair competition: MLCP protects pCPI-17 from other phosphatases, while pCPI-17 blocks other substrates from MLCP’s active site. MLCP dephosphorylates pCPI-17 at a slow rate that is, nonetheless, both sufficient and necessary to explain the speed of pCPI-17 dephosphorylation and the consequent MLCP activation during muscle relaxation.

Cardiac Hypertrophy in Transgenic Mice with Overexpressed Small-Subunit of Human Myosin Light Chain Phosphatase

2003 ◽  
Vol 33 (12) ◽  
pp. 1165
Author(s):  
Sung Won Bae ◽  
Won Ha Lee ◽  
Chul Hong Kim ◽  
Haing Kee Park ◽  
Sang Chol Lee ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
Cardiac Hypertrophy ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Small Subunit ◽  
Myosin Light Chain Phosphatase

scholarly journals Abnormal myosin phosphatase targeting subunit 1 phosphorylation and actin polymerization contribute to impaired myogenic regulation of cerebral arterial diameter in the type 2 diabetic Goto-Kakizaki rat

2016 ◽  
Vol 37 (1) ◽  
pp. 227-240 ◽  
Author(s):  
Khaled S Abd-Elrahman ◽  
Olaia Colinas ◽  
Emma J Walsh ◽  
Hai-Lei Zhu ◽  
Christine M Campbell ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Light Chain ◽  
Actin Polymerization ◽  
Myosin Light Chain ◽  
Intraluminal Pressure ◽  
Myogenic Response ◽  
Myosin Phosphatase ◽  
Myosin Light Chain Phosphatase ◽  
Myogenic Regulation

The myogenic response of cerebral resistance arterial smooth muscle to intraluminal pressure elevation is a key physiological mechanism regulating blood flow to the brain. Rho-associated kinase plays a critical role in the myogenic response by activating Ca2+ sensitization mechanisms: (i) Rho-associated kinase inhibits myosin light chain phosphatase by phosphorylating its targeting subunit myosin phosphatase targeting subunit 1 (at T855), augmenting 20 kDa myosin regulatory light chain (LC20) phosphorylation and force generation; and (ii) Rho-associated kinase stimulates cytoskeletal actin polymerization, enhancing force transmission to the cell membrane. Here, we tested the hypothesis that abnormal Rho-associated kinase-mediated myosin light chain phosphatase regulation underlies the dysfunctional cerebral myogenic response of the Goto-Kakizaki rat model of type 2 diabetes. Basal levels of myogenic tone, LC20, and MYPT1-T855 phosphorylation were elevated and G-actin content was reduced in arteries of pre-diabetic 8–10 weeks Goto-Kakizaki rats with normal serum insulin and glucose levels. Pressure-dependent myogenic constriction, LC20, and myosin phosphatase targeting subunit 1 phosphorylation and actin polymerization were suppressed in both pre-diabetic Goto-Kakizaki and diabetic (18–20 weeks) Goto-Kakizaki rats, whereas RhoA, ROK2, and MYPT1 expression were unaffected. We conclude that abnormal Rho-associated kinase-mediated Ca2+ sensitization contributes to the dysfunctional cerebral myogenic response in the Goto-Kakizaki model of type 2 diabetes.

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