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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2002-7-23
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pubmed:abstractText |
The endothelin B receptor (ETBR) has been shown to mediate autoinduction of endothelin-1 (ET-1). We previously reported that the ET(B)R interacts with Galpha13, a member of the heterotrimeric GTP-binding protein family. In the present study, we examined whether Galpha13 induces preproET-1 (ppET-1) gene transcription, which could result in ET-1 autoinduction in a renal epithelial cell line. We generated a reporter gene construct under control of the ppET-1 promoter region. The construct was transiently expressed in COS-7 cells. Transient expression of ETBR increased the promoter activity of ppET-1 following treatment with 100 nmol/l of ET-1. Expression of Galpha13Q226L or Galpha9209L, constitutively active forms of Galpha13 and Galpha9, also activated the ppET-1 promoter. ETBR-stimulated ppET-1 promoter activity was partially diminished by the expression of dominant negative forms of c-Jun N-terminal kinase (JNK1APF) or MAPK/ERK kinase (MEKK97M). Expression of JNK1APF also inhibited Galpha13Q226L-induced ppET-1 promoter activation. These findings indicate that Galpha13 can induce ppET-1 gene expression through a JNK-mediated pathway. Our results also suggest that this Galpha13-coupled signaling pathway may play an important role in a sustained ET-1 autoinduction loop in various pathophysiological conditions.
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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/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelin-1,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelins,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Heterotrimeric GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 8,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Endothelin B,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Endothelin
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0916-9636
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
25
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
427-32
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:12135322-Animals,
pubmed-meshheading:12135322-COS Cells,
pubmed-meshheading:12135322-DNA-Binding Proteins,
pubmed-meshheading:12135322-Endothelin-1,
pubmed-meshheading:12135322-Endothelins,
pubmed-meshheading:12135322-GTP-Binding Protein alpha Subunits, G12-G13,
pubmed-meshheading:12135322-GTP-Binding Protein alpha Subunits, Gq-G11,
pubmed-meshheading:12135322-Gene Expression Regulation,
pubmed-meshheading:12135322-Heterotrimeric GTP-Binding Proteins,
pubmed-meshheading:12135322-Humans,
pubmed-meshheading:12135322-Mitogen-Activated Protein Kinase 8,
pubmed-meshheading:12135322-Mitogen-Activated Protein Kinases,
pubmed-meshheading:12135322-Promoter Regions, Genetic,
pubmed-meshheading:12135322-Protein Precursors,
pubmed-meshheading:12135322-Receptor, Endothelin B,
pubmed-meshheading:12135322-Receptors, Endothelin
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pubmed:year |
2002
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pubmed:articleTitle |
Galpha13 induces preproET-1 gene expression via JNK.
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pubmed:affiliation |
Third Department of Internal Medicine, Kumamoto University School of Medicine, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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