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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2001-5-23
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pubmed:abstractText |
We used a cultured murine cell model of the inner medullary collecting duct (mIMCD-3 cells) to examine the regulation of the ubiquitous sodium-proton exchanger, Na+/H+ exchanger isoform 1 (NHE-1), by a prototypical G protein-coupled receptor, the bradykinin B2 receptor. Bradykinin rapidly activates NHE-1 in a concentration-dependent manner as assessed by proton microphysiometry of quiescent cells and by 2'-7'-bis[2-carboxymethyl]-5(6)-carboxyfluorescein fluorescence measuring the accelerated rate of pH(i) recovery from an imposed acid load. The activation of NHE-1 is blocked by inhibitors of the bradykinin B2 receptor, phospholipase C, Ca2+/calmodulin (CaM), and Janus kinase 2 (Jak2), but not by pertussis toxin or by inhibitors of protein kinase C and phosphatidylinositol 3'-kinase. Immunoprecipitation studies showed that bradykinin stimulates the assembly of a signal transduction complex that includes CaM, Jak2, and NHE-1. CaM appears to be a direct substrate for phosphorylation by Jak2 as measured by an in vitro kinase assay. We propose that Jak2 is a new indirect regulator of NHE-1 activity, which modulates the activity of NHE-1 by increasing the tyrosine phosphorylation of CaM and most likely by increasing the binding of CaM to NHE-1.
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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/Bradykinin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calmodulin,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Jak2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Janus Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Pertussis Toxin,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Bradykinin B2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Bradykinin,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Hydrogen Antiporter,
http://linkedlifedata.com/resource/pubmed/chemical/Type C Phospholipases,
http://linkedlifedata.com/resource/pubmed/chemical/Virulence Factors, Bordetella,
http://linkedlifedata.com/resource/pubmed/chemical/growth factor-activatable Na-H...
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
pubmed-author:BellJ LJL,
pubmed-author:CollinsworthGG,
pubmed-author:FitzgibbonWW,
pubmed-author:GarnovskayaM NMN,
pubmed-author:JaffaA AAA,
pubmed-author:MukhinY VYV,
pubmed-author:PettusTT,
pubmed-author:PlothD WDW,
pubmed-author:RaymondJ RJR,
pubmed-author:TholanikunnelB GBG,
pubmed-author:VlasovaTT
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pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
276
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
17339-46
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11278760-Animals,
pubmed-meshheading:11278760-Bradykinin,
pubmed-meshheading:11278760-Calcium,
pubmed-meshheading:11278760-Calmodulin,
pubmed-meshheading:11278760-Cell Line,
pubmed-meshheading:11278760-Enzyme Inhibitors,
pubmed-meshheading:11278760-Hydrogen-Ion Concentration,
pubmed-meshheading:11278760-Janus Kinase 2,
pubmed-meshheading:11278760-Kidney Medulla,
pubmed-meshheading:11278760-Kinetics,
pubmed-meshheading:11278760-Mice,
pubmed-meshheading:11278760-Mice, Transgenic,
pubmed-meshheading:11278760-Models, Biological,
pubmed-meshheading:11278760-Pertussis Toxin,
pubmed-meshheading:11278760-Protein-Tyrosine Kinases,
pubmed-meshheading:11278760-Proto-Oncogene Proteins,
pubmed-meshheading:11278760-Receptor, Bradykinin B2,
pubmed-meshheading:11278760-Receptors, Bradykinin,
pubmed-meshheading:11278760-Signal Transduction,
pubmed-meshheading:11278760-Simian virus 40,
pubmed-meshheading:11278760-Sodium,
pubmed-meshheading:11278760-Sodium-Hydrogen Antiporter,
pubmed-meshheading:11278760-Transcription, Genetic,
pubmed-meshheading:11278760-Type C Phospholipases,
pubmed-meshheading:11278760-Virulence Factors, Bordetella
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pubmed:year |
2001
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pubmed:articleTitle |
Bradykinin B2 receptors activate Na+/H+ exchange in mIMCD-3 cells via Janus kinase 2 and Ca2+/calmodulin.
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pubmed:affiliation |
Medical and Research Services of the Ralph H. Johnson Veterans Affairs Medical Center, and Department of Medicine of the Medical University of South Carolina, Charleston, South Carolina 29425, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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