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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
14
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pubmed:dateCreated |
2000-5-8
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pubmed:abstractText |
Myosin light chain phosphatase (MLCP) plays a pivotal role in smooth muscle contraction by regulating Ca(2+) sensitivity of myosin light chain phosphorylation. A smooth muscle phosphoprotein called CPI-17 specifically and potently inhibits MLCP in vitro and in situ and is activated when phosphorylated at Thr-38, which increases its inhibitory potency 1000-fold. We produced a phosphospecific antibody for this site in CPI-17 and used it to study in situ phosphorylation of endogenous CPI-17 in arterial smooth muscle in response to agonist stimulation. In the intact femoral artery, CPI-17 phosphorylation was negligible at the resting state and was not increased during contraction induced by K(+) depolarization. The Ca(2+)-sensitizing agonists histamine and phenylephrine induced nearly equivalent contractions, but histamine generated significantly higher levels of CPI-17 phosphorylation. In alpha-toxin-permeabilized strips at pCa 6.7, contractile force and CPI-17 phosphorylation were proportional in response to histamine, guanosine 5'-O-(gamma-thiotriphosphate), and histamine plus guanyl-5'-yl thiophosphate, implying that histamine increased CPI-17 phosphorylation through activation of G proteins. Inhibitors of Rho-kinase (Y27632) and protein kinase C (PKC; GF109203X) reduced contraction and CPI-17 phosphorylation in parallel, suggesting that CPI-17 functions downstream of Rho kinases and PKC. The results show that agonists such as histamine signal through phosphorylation of CPI-17 to produce Ca(2+) sensitization of smooth muscle contraction.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amides,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate),
http://linkedlifedata.com/resource/pubmed/chemical/Histamine,
http://linkedlifedata.com/resource/pubmed/chemical/Indoles,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Maleimides,
http://linkedlifedata.com/resource/pubmed/chemical/Muscle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Myosin-Light-Chain Phosphatase,
http://linkedlifedata.com/resource/pubmed/chemical/Phenylephrine,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoprotein Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase C,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Pyridines,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/Y 27632,
http://linkedlifedata.com/resource/pubmed/chemical/bisindolylmaleimide I,
http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
275
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9897-900
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:10744661-Amides,
pubmed-meshheading:10744661-Animals,
pubmed-meshheading:10744661-Cell Membrane Permeability,
pubmed-meshheading:10744661-Enzyme Inhibitors,
pubmed-meshheading:10744661-Femoral Artery,
pubmed-meshheading:10744661-GTP-Binding Proteins,
pubmed-meshheading:10744661-Guanosine 5'-O-(3-Thiotriphosphate),
pubmed-meshheading:10744661-Histamine,
pubmed-meshheading:10744661-Indoles,
pubmed-meshheading:10744661-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:10744661-Maleimides,
pubmed-meshheading:10744661-Muscle, Smooth, Vascular,
pubmed-meshheading:10744661-Muscle Contraction,
pubmed-meshheading:10744661-Muscle Proteins,
pubmed-meshheading:10744661-Myosin-Light-Chain Phosphatase,
pubmed-meshheading:10744661-Phenylephrine,
pubmed-meshheading:10744661-Phosphoprotein Phosphatases,
pubmed-meshheading:10744661-Phosphoproteins,
pubmed-meshheading:10744661-Phosphorylation,
pubmed-meshheading:10744661-Protein Kinase C,
pubmed-meshheading:10744661-Protein-Serine-Threonine Kinases,
pubmed-meshheading:10744661-Pyridines,
pubmed-meshheading:10744661-Rabbits,
pubmed-meshheading:10744661-Type C Phospholipases,
pubmed-meshheading:10744661-rho-Associated Kinases
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pubmed:year |
2000
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pubmed:articleTitle |
Agonists trigger G protein-mediated activation of the CPI-17 inhibitor phosphoprotein of myosin light chain phosphatase to enhance vascular smooth muscle contractility.
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pubmed:affiliation |
Department of Physiology and Biophysics, Georgetown University Medical Center, Washington, DC 20007, USA. tkitaz01@gusun.georgetown.edu
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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