NDLI: Regulation of basal LC20 phosphorylation by MYPT1 and CPI-17 in murine gastric antrum, gastric fundus, and proximal colon smooth muscles

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Regulation of basal LC20 phosphorylation by MYPT1 and CPI-17 in murine gastric antrum, gastric fundus, and proximal colon smooth muscles

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Bhetwal, B. P. An, C. L. Fisher, S. A. Perrino, B. A.
Description	Country affiliation: United States Author Affiliation: Bhetwal BP ( Department of Physiology & Cell Biology, Center of Biomedical Research Excellence, University of Nevada School of Medicine, 1664 N Virginia St., Reno, NV 89557, USA.)
Abstract	BACKGROUND: Myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) govern myosin light chain (LC20) phosphorylation and smooth muscle contraction. Rho kinase (ROK) inhibits MLCP, resulting in greater LC20 phosphorylation and force generation at a given [Ca(2+) ](i) . Here, we investigate the role of ROK in regulating LC20 phosphorylation and spontaneous contractions of gastric fundus, gastric antrum, and proximal colon smooth muscles. METHODS: Protein and phosphorylation levels were determined by western blotting. The effects of Y27632, nicardipine, and GF109203X on phosphorylation levels and contraction were measured. KEY RESULTS: Î³-Actin expression is similar in all three smooth muscles. LC20 and pS19 are highest, but ROK1 and ROK2 are lowest, in antrum and proximal colon smooth muscles. LZ +/- myosin phosphatase targeting subunit 1 (MYPT1), CPI-17, and pT696, pT853, and pT38 are highest in fundus and proximal colon smooth muscles. Myosin phosphatase-rho interacting protein (M-RIP) expression is lowest in fundus, and highest in antrum and proximal colon smooth muscles. Y27632 reduced pT853 in each smooth muscle, but reduced pT696 only in fundus smooth muscles. Nicardipine had no effect on pT38 in each smooth muscle, while GF109203X reduced pT38 in proximal colon and fundus smooth muscles. Y27632 or nicardipine reduced pS19 in proximal colon and fundus smooth muscles. Y27632 or nicardipine inhibited antrum and proximal colon smooth muscle spontaneous contractions, but only Y27632 reduced fundus smooth muscle tone. Zero external Ca(2+) relaxed each smooth muscle and abolished LC20 phosphorylation. CONCLUSIONS & INFERENCES: Organ-specific mechanisms involving the MLCP interacting proteins LZ +/- MYPT1, M-RIP, and CPI-17 are critical to regulating basal LC20 phosphorylation in gastrointestinal smooth muscles.
File Format	HTM / HTML
ISSN	13501925
e-ISSN	13652982
DOI	10.1111/j.1365-2982.2011.01769.x
Journal	Neurogastroenterology & Motility
Issue Number	10
Volume Number	23
Language	English
Publisher	Wiley-Blackwell
Publisher Date	2011-10-01
Publisher Place	Great Britain (UK)
Access Restriction	Open
Subject Keyword	Discipline Neurogastroenterology Gastrointestinal Tract Metabolism Muscle Proteins Muscle, Smooth Myosin-light-chain Kinase Phosphoproteins Smooth Muscle Myosins Animals Blotting, Western Colon Electrophoresis, Polyacrylamide Gel Gastric Fundus Gene Expression Mice Mice, Inbred C57bl Microfilament Proteins Myosin-light-chain Phosphatase Phosphorylation Pyloric Antrum Research Support, N.i.h., Extramural
Content Type	Text
Resource Type	Article
Subject	Physiology Endocrine and Autonomic Systems Gastroenterology

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Regulation of basal LC20 phosphorylation by MYPT1 and CPI-17 in murine gastric antrum, gastric fundus, and proximal colon smooth muscles

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Regulation of basal LC20 phosphorylation by MYPT1 and CPI-17 in murine gastric antrum, gastric fundus, and proximal colon smooth muscles

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Regulation of basal LC20 phosphorylation by MYPT1 and CPI-17 in murine gastric antrum, gastric fundus, and proximal colon smooth muscles