Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-9-9
pubmed:abstractText
This article describes a novel method to access functional interactions of two defective mutant receptors. As a model, luteinizing hormone receptor, a G-protein-coupled receptor, was used by coexpressing two different mutants, one defective in hormone binding and the other defective in signal generation. When these two mutants were coexpressed in a cell, the cell responded to the hormone and induced the hormone action, indicating the interaction of the two receptors and rescue of the activity. The luteinizing hormone receptor consists of a 350-amino-acid extracellular N-terminal domain (exodomain), followed by seven transmembrane domains and connecting loops (endodomain). Hormone binds to the exodomain, whereas hormone signals are generated in the endodomain. Here, we show that binding of hormone to one receptor can activate adenylyl cyclase through its transmembrane bundle, intramolecular activation (cis-activation), as well as intermolecular activation (trans-activation) through the transmembrane bundle of an adjacent receptor, without forming a stable receptor dimer. Our observations provide new insights into the mechanism of receptor activation mechanisms, and have implications for the treatment of inherited disorders of glycoprotein hormone receptors.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1046-2023
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
318-23
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Use of defined-function mutants to access receptor-receptor interactions.
pubmed:affiliation
Department of Chemistry, University of Kentucky, 40506-0055, Lexington, KY, USA
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.