Linked Life Data

15331590

Source:http://linkedlifedata.com/resource/pubmed/id/15331590

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
45
pubmed:dateCreated
2004-11-1
pubmed:abstractText
Down-regulation is a classic response of most G protein-coupled receptors to prolonged agonist stimulation. We recently showed that when expressed in baby hamster kidney cells, the human beta1-but not the beta2-adrenergic receptor (AR) is totally resistant to agonist-mediated down-regulation, whereas both have similar rates of basal degradation (Liang, W., Austin, S., Hoang, Q., and Fishman, P. H. (2003) J. Biol. Chem. 278, 39773-39781). To identify the underlying mechanism(s) for this resistance, we investigated the role of proteasomes, lysosomes, and ubiquitination in the degradation of beta1AR expressed in baby hamster kidney and human embryonic kidney 293 cells. Both lysosomal and proteasomal inhibitors reduced beta1AR degradation in agonist-stimulated cells but were less effective on basal degradation. To determine whether beta1AR trafficked to lysosomes we used confocal fluorescence microscopy. We observed some colocalization of beta1AR and lysosomal markers in agonist-treated cells but much less than that of beta2AR even in cells co-transfected with arrestin-2, which increases beta1AR internalization. Ubiquitination of beta2AR readily occurred in agonist-stimulated cells, whereas ubiquitination of beta1AR was not detectable even under conditions optimal for that of beta2AR. Moreover, in cells expressing betaAR chimeras in which the C termini have been switched, the chimeric beta1AR with beta2AR C-tail underwent ubiquitination and down-regulation, but the chimeric beta2AR with beta1AR C-tail did not. Our results demonstrate for the first time that beta1AR and beta2AR differ in the ability to be ubiquitinated. Because ubiquitin serves as a signal for sorting membrane receptors to lysosomes, the lack of agonist-mediated ubiquitination of beta1AR may prevent its extensive trafficking to lysosomes and, thus, account for its resistance to down-regulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
5
pubmed:volume
279
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
46882-9
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed-meshheading:15331590-Acetylcysteine, pubmed-meshheading:15331590-Animals, pubmed-meshheading:15331590-Arrestin, pubmed-meshheading:15331590-Cell Line, pubmed-meshheading:15331590-Cricetinae, pubmed-meshheading:15331590-Down-Regulation, pubmed-meshheading:15331590-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:15331590-Endocytosis, pubmed-meshheading:15331590-Humans, pubmed-meshheading:15331590-Lysosomes, pubmed-meshheading:15331590-Microscopy, Confocal, pubmed-meshheading:15331590-Proteasome Endopeptidase Complex, pubmed-meshheading:15331590-Protein Binding, pubmed-meshheading:15331590-Protein Structure, Tertiary, pubmed-meshheading:15331590-Receptors, Adrenergic, beta-1, pubmed-meshheading:15331590-Receptors, Adrenergic, beta-2, pubmed-meshheading:15331590-Time Factors, pubmed-meshheading:15331590-Transfection, pubmed-meshheading:15331590-Ubiquitin
pubmed:year
2004
pubmed:articleTitle
Resistance of the human beta1-adrenergic receptor to agonist-induced ubiquitination: a mechanism for impaired receptor degradation.
pubmed:affiliation
Membrane Biochemistry Section, Laboratory of Molecular and Cellular Neurobiology, NINDS, National Institutes of Health, Bethesda, Maryland 20892, USA.
pubmed:publicationType
Journal Article