Linked Life Data

9843382

Source:http://linkedlifedata.com/resource/pubmed/id/9843382

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
1998-12-21
pubmed:abstractText
Accumulating evidence suggests that G protein-coupled receptors (GPCRs) can form dimeric or oligomeric arrays. Based on this concept, we have tested the hypothesis that truncated GPCRs can act as negative regulators of wild-type receptor function. Using the GS-coupled V2 vasopressin receptor as a model system, we systematically analyzed the ability of N- and C-terminal V2 receptor fragments to interfere with the activity of the wild-type V2 receptor coexpressed in COS-7 cells. Several N-terminal V2 receptor truncation mutants were identified that strongly inhibited the function (as determined in cAMP and radioligand binding assays) and cell surface trafficking of the coexpressed full-length V2 receptor. However, these truncation mutants did not interfere with the function of other GS-coupled receptors such as the D1 dopamine and the beta2-adrenergic receptors. Dominant negative effects were only observed with mutant receptors that contained at least three transmembrane domains. In addition, immunoblotting experiments showed that all V2 receptor truncation mutants displaying dominant negative activity (but not those mutant receptors lacking this activity) were able to form heterodimers with the full-length V2 receptor, suggesting that complex formation between mutant and wild-type V2 receptors underlies the observed inhibition of wild-type receptor function. Given the high degree of structural homology shared by all GPCRs, our findings should also be applicable to other members of this receptor superfamily.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
15773-84
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Truncated V2 vasopressin receptors as negative regulators of wild-type V2 receptor function.
pubmed:affiliation
Laboratory of Bioorganic Chemistry, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article