Linked Life Data

7507928

Source:http://linkedlifedata.com/resource/pubmed/id/7507928

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1994-3-4
pubmed:abstractText
An aromatic residue, tyrosine 326 in the prototypical human beta 2-adrenergic receptor, exists in a highly conserved sequence motif in virtually all members of the G protein-coupled receptor family. The potential role of this conserved aromatic amino acid residue in the cellular processes of sequestration (a rapid internalization of the surface receptor) and down-regulation (a slower loss of total cellular receptors) associated with agonist-mediated desensitization of the beta 2-adrenergic receptor was assessed by replacing tyrosine residue 326 with an alanine residue (beta 2AR-Y326A). This mutation completely abolishes agonist-mediated receptor sequestration without affecting the ability of the receptor to activate maximally adenylyl cyclase, to undergo rapid desensitization, and to down-regulate in response to agonist. The only other major change associated with the mutated receptor is a complete loss of the ability to resensitize following rapid desensitization. These results imply that this tyrosine residue, which is part of a highly conserved sequence motif in G protein-coupled receptors, may be responsible for their agonist-mediated sequestration and that sequestration and down-regulation of the receptor are dissociable phenomena. The lack of resensitization in the sequestration-defective beta 2-adrenergic receptor mutant strongly suggests that the sequestration pathway is an important mechanism by which cells re-establish the normal responsiveness of G protein-coupled receptors following the removal of agonist.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
269
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2790-5
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:7507928-Alanine, pubmed-meshheading:7507928-Amino Acid Sequence, pubmed-meshheading:7507928-Animals, pubmed-meshheading:7507928-CHO Cells, pubmed-meshheading:7507928-Conserved Sequence, pubmed-meshheading:7507928-Cricetinae, pubmed-meshheading:7507928-Down-Regulation, pubmed-meshheading:7507928-Epitopes, pubmed-meshheading:7507928-GTP-Binding Proteins, pubmed-meshheading:7507928-Humans, pubmed-meshheading:7507928-Iodocyanopindolol, pubmed-meshheading:7507928-Isoproterenol, pubmed-meshheading:7507928-Kinetics, pubmed-meshheading:7507928-Molecular Sequence Data, pubmed-meshheading:7507928-Multigene Family, pubmed-meshheading:7507928-Mutagenesis, Site-Directed, pubmed-meshheading:7507928-Pindolol, pubmed-meshheading:7507928-Polymerase Chain Reaction, pubmed-meshheading:7507928-Protein Conformation, pubmed-meshheading:7507928-Radioligand Assay, pubmed-meshheading:7507928-Receptors, Adrenergic, beta-2, pubmed-meshheading:7507928-Receptors, Cell Surface, pubmed-meshheading:7507928-Sequence Homology, Amino Acid, pubmed-meshheading:7507928-Transfection, pubmed-meshheading:7507928-Tyrosine
pubmed:year
1994
pubmed:articleTitle
A highly conserved tyrosine residue in G protein-coupled receptors is required for agonist-mediated beta 2-adrenergic receptor sequestration.
pubmed:affiliation
Howard Hughes Medical Institute Laboratories, Duke University Medical Center, Durham, North Carolina 27710.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't