Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2000-4-12
pubmed:abstractText
Cell surface receptor activation generally leads to changes in mRNA abundance, which may involve regulatory targets in processes working at the post-transcriptional level. Many types of agonists down-regulate vascular smooth muscle angiotensin receptor (AT(1)-R) gene expression, but it is unclear which of these activate post-transcriptional mechanisms. To reconstitute faithfully the normal AT(1)-R mRNA regulatory environment, tetracycline-suppressible promoters drive highly accurate recombinant AT(1)-R mRNA mimics in vascular smooth muscle cells that co-express an endogenous AT(1)-R mRNA. Down-regulation of the latter occurs shortly after stimulating mitogenic receptors or by using forskolin, but only cAMP signaling reduces expression of the recombinant AT(1)-R mRNA. Transcription of the recombinant mRNA is unaffected by cAMP signaling. Deletions of the AT(1)-R mRNA 3'-untranslated region do not impair cAMP-mediated down-regulation. Both loss of function and gain of function mutants show the response is mediated by the 5'-untranslated region. These observations provide the first direct functional evidence for modulation of vascular AT(1)-R gene expression by a mechanism involving a protein kinase A-regulated post-transcriptional process.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7604-11
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:10713068-Animals, pubmed-meshheading:10713068-Aorta, pubmed-meshheading:10713068-Cells, Cultured, pubmed-meshheading:10713068-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:10713068-Down-Regulation, pubmed-meshheading:10713068-Forskolin, pubmed-meshheading:10713068-Half-Life, pubmed-meshheading:10713068-Mitogens, pubmed-meshheading:10713068-Mitosis, pubmed-meshheading:10713068-Muscle, Smooth, Vascular, pubmed-meshheading:10713068-Mutation, pubmed-meshheading:10713068-RNA, Messenger, pubmed-meshheading:10713068-RNA Processing, Post-Transcriptional, pubmed-meshheading:10713068-RNA Stability, pubmed-meshheading:10713068-Rats, pubmed-meshheading:10713068-Receptor, Angiotensin, Type 1, pubmed-meshheading:10713068-Receptor, Angiotensin, Type 2, pubmed-meshheading:10713068-Receptors, Angiotensin, pubmed-meshheading:10713068-Signal Transduction, pubmed-meshheading:10713068-Tetracyclines, pubmed-meshheading:10713068-Untranslated Regions
pubmed:year
2000
pubmed:articleTitle
Reconstitution of angiotensin receptor mRNA down-regulation in vascular smooth muscle. Post-transcriptional control by protein kinase a but not mitogenic signaling directed by the 5'-untranslated region.
pubmed:affiliation
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't