Linked Life Data

11726668

Source:http://linkedlifedata.com/resource/pubmed/id/11726668

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2002-3-4
pubmed:abstractText
beta-Arrestins have been implicated in regulating internalization of the parathyroid hormone receptor (PTHR), but the structural features in the receptor required for this effect are unknown. In the present study performed in HEK-293 cells, we demonstrated that different topological domains of PTHR are implicated in agonist-dependent receptor internalization; truncation of the cytoplasmic tail (PTHR-TR), selective mutations of the cytoplasmic tail to remove the sites of parathyroid hormone (PTH)-stimulated phosphorylation (PTHR-PD), and mutations in the third transmembrane helix (N289A) or in the third cytoplasmic loop (K382A) resulted in a 30-60% reduction in (125)I-PTH-related protein internalization. To better define the role of these internalization determinants, we have tested the ability of these mutant PTHRs to associate with beta-arrestins by using three different methodological approaches: 1) ability of overexpression of beta-arrestins to restore the internalization of (125)I-PTH-related protein for the mutant PTHRs; 2) visualization of PTH-mediated trafficking of beta-arrestin1 and -2 fused to the green fluorescent protein with receptors by confocal microscopy; 3) quantification of beta-arrestin1-green fluorescent protein translocation by Western blot. Our data reveal that the receptor' cytoplasmic tail contains determinants of beta-arrestin interaction that are distinct from the phosphorylation sites and are sufficient for transient association of beta-arrestin2, but stable association requires receptor phosphorylation. Determinants in the receptor's core (Asn-289 and Lys-382) appear to regulate internalization of the receptor/beta-arrestin complex toward early endocytic endosomes during the initial step of endocytosis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
8121-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11726668-Arrestins, pubmed-meshheading:11726668-Asparagine, pubmed-meshheading:11726668-Blotting, Western, pubmed-meshheading:11726668-Cell Line, pubmed-meshheading:11726668-Cell Membrane, pubmed-meshheading:11726668-Cyclic AMP, pubmed-meshheading:11726668-Cytoplasm, pubmed-meshheading:11726668-DNA, Complementary, pubmed-meshheading:11726668-Endocytosis, pubmed-meshheading:11726668-Green Fluorescent Proteins, pubmed-meshheading:11726668-Humans, pubmed-meshheading:11726668-Immunoblotting, pubmed-meshheading:11726668-Kinetics, pubmed-meshheading:11726668-Ligands, pubmed-meshheading:11726668-Luminescent Proteins, pubmed-meshheading:11726668-Lysine, pubmed-meshheading:11726668-Microscopy, Confocal, pubmed-meshheading:11726668-Mutation, pubmed-meshheading:11726668-Phosphorylation, pubmed-meshheading:11726668-Protein Binding, pubmed-meshheading:11726668-Protein Structure, Tertiary, pubmed-meshheading:11726668-Protein Transport, pubmed-meshheading:11726668-Receptors, Parathyroid Hormone, pubmed-meshheading:11726668-Signal Transduction, pubmed-meshheading:11726668-Time Factors
pubmed:year
2002
pubmed:articleTitle
Internalization determinants of the parathyroid hormone receptor differentially regulate beta-arrestin/receptor association.
pubmed:affiliation
Department of Pharmacology, Institute of Pharmacology and Toxicology, University of Wuerzburg, Wuerzburg D-97078, Germany.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't