Myosin Light Chain Phosphatase (Myosin Phosphatase)

2002 ◽  
Author(s):  
David J. Hartshorne
Keyword(s):  
Light Chain ◽  
Myosin Light Chain ◽  
Myosin Phosphatase ◽  
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.

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.

scholarly journals Arachidonic acid inhibits myosin light chain phosphatase and sensitizes smooth muscle to calcium.

1992 ◽  
Vol 267 (30) ◽  
pp. 21492-21498
Author(s):  
M.C. Gong ◽  
A Fuglsang ◽  
D Alessi ◽  
S Kobayashi ◽  
P Cohen ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Myosin Light Chain Phosphatase

scholarly journals A Novel Regulatory Mechanism of Myosin Light Chain Phosphorylation via Binding of 14-3-3 to Myosin Phosphatase

2008 ◽  
Vol 19 (3) ◽  
pp. 1062-1071 ◽  
Author(s):  
Yasuhiko Koga ◽  
Mitsuo Ikebe
Keyword(s):  
Light Chain ◽  
Myosin Light Chain ◽  
Regulatory Mechanism ◽  
Kinase Inhibitor ◽  
Myosin Ii ◽  
Critical Role ◽  
Rho Kinase ◽  
Myosin Phosphatase ◽  
Dependent Cell ◽  
Direct Binding

Myosin II phosphorylation–dependent cell motile events are regulated by myosin light-chain (MLC) kinase and MLC phosphatase (MLCP). Recent studies have revealed myosin phosphatase targeting subunit (MYPT1), a myosin-binding subunit of MLCP, plays a critical role in MLCP regulation. Here we report the new regulatory mechanism of MLCP via the interaction between 14-3-3 and MYPT1. The binding of 14-3-3β to MYPT1 diminished the direct binding between MYPT1 and myosin II, and 14-3-3β overexpression abolished MYPT1 localization at stress fiber. Furthermore, 14-3-3β inhibited MLCP holoenzyme activity via the interaction with MYPT1. Consistently, 14-3-3β overexpression increased myosin II phosphorylation in cells. We found that MYPT1 phosphorylation at Ser472 was critical for the binding to 14-3-3. Epidermal growth factor (EGF) stimulation increased both Ser472 phosphorylation and the binding of MYPT1-14-3-3. Rho-kinase inhibitor inhibited the EGF-induced Ser472 phosphorylation and the binding of MYPT1-14-3-3. Rho-kinase specific siRNA also decreased EGF-induced Ser472 phosphorylation correlated with the decrease in MLC phosphorylation. The present study revealed a new RhoA/Rho-kinase–dependent regulatory mechanism of myosin II phosphorylation by 14-3-3 that dissociates MLCP from myosin II and attenuates MLCP activity.

Modulation of uterine resistance artery lumen diameter by calcium and G protein activation during pregnancy

1994 ◽  
Vol 267 (3) ◽  
pp. H952-H961 ◽  
Author(s):  
G. D'Angelo ◽  
G. Osol
Keyword(s):  
Smooth Muscle ◽  
G Protein ◽  
G Proteins ◽  
Light Chain ◽  
Myosin Light Chain ◽  
Lumen Diameter ◽  
Maximal Response ◽  
Adrenergic Stimulation ◽  
Myosin Light Chain Phosphatase ◽  
Arterial Lumen

The purpose of this study was to determine whether the increased sensitivity of uterine resistance arteries from late pregnant (LP) rats to alpha-adrenergic stimulation is due to an alteration in the fundamental relationship between cytosolic calcium (Ca2+) and arterial lumen diameter. Uterine arcuate arteries were permeabilized with Staphylococcus aureus alpha-toxin under optimal conditions and constricted to varying degrees with discrete Ca2+ concentrations at a distending pressure of 50 mmHg. Arterial segments from nonpregnant (NP) and LP rats exhibited similar Ca2+/lumen diameter characteristics. Ca2+ (0.1 microM) produced appreciable constriction, and lumen diameter decreased steeply between 0.175 and 0.25 microM Ca2+; maximal responses were attained with 0.5 microM Ca2+. Activation of guanine nucleotide binding proteins (G proteins) with guanosine 5'-triphosphate (GTP; 1-100 microM), as reportedly occurs during alpha-adrenergic stimulation, potentiated the Ca(2+)-induced constriction by 121 and 79% in arteries from LP and NP rats, respectively. No significant differences between the two animal groups were noted. Guanosine 5'-O-(gamma-thiotriphosphate) (GTP gamma S; 0.1-10 microM), a nonhydrolyzable analogue of GTP, effected a larger potentiating effect over that maximal response caused by GTP in arteries from NP rats. Ca(2+)- and Ca2+/GTP-induced constrictions were more potently reversed by guanosine 5'-O-(beta-thiodiphosphate) (GDP beta S)., a competitive inhibitor of GTP, in arteries from NP rats. These data suggest that pregnancy-induced increases in sensitivity to alpha-adrenergic stimulation may be related to altered G protein cycling rates, such that G proteins in smooth muscle cells in arcuate arteries from NP rats are more susceptible to deactivation. Alternatively, consistent with the model of G protein-mediated inhibition of myosin light chain phosphatase, myosin light chain phosphatase activity may be enhanced in uterine vascular smooth muscle from NP rats relative to that from LP rats.

Sign in / Sign up

Export Citation Format

Share Document