Linked Life Data

8063694

Source:http://linkedlifedata.com/resource/pubmed/id/8063694

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
33
pubmed:dateCreated
1994-9-21
pubmed:abstractText
An essential role of the conserved Asp74 in the coupling of the type 1 angiotensin II (AII) receptor (AT1) to phospholipase C has already been reported (Bihoreau, C., Monnot, C., Davies, E., Teutsch, B., Bernstein, K. B., Corvol, P., and Clauser, E. (1993) Proc. Natl. Acad. Sci. U. S. A. 90, 5133-5137). Moreover, preliminary modeling studies have shown that a spatial proximity exists between Asp74, located in transmembrane domain II, and Tyr292, located in transmembrane domain VII and conserved in many, but not all, G protein-coupled receptors. We mutated Tyr292 into Phe and evaluated the pharmacological and activation characteristics of the mutated receptor (Y292F) stably expressed in Chinese hamster ovary cells. This receptor possessed unchanged binding properties for agonist or antagonist peptide ligands compared to the wild-type receptor, while its coupling to phospholipase C was severely impaired. Interestingly, competition binding experiments, using 125I-[Sar1]AII as a tracer ligand, showed that the Y292F receptor displayed an increased Ki value for DuP 753, an AT1-specific nonpeptide antagonist and a greatly decreased Ki value for the AT2-specific ligand CGP 42112A. These pharmacological changes are similar to those observed for the previously reported mutation of Asp74 into Asn. This apparently symmetrical role of Asp74 and Tyr292 is consistent with the hypothesis that an interaction between these two amino acids could be a key event in the molecular processes linking AII recognition and AT1 receptor activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
19
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
20815-8
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Tyr292 in the seventh transmembrane domain of the AT1A angiotensin II receptor is essential for its coupling to phospholipase C.
pubmed:affiliation
INSERM, Unité 401, CCIPE, Montpellier, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't