Linked Life Data

11597573

Source:http://linkedlifedata.com/resource/pubmed/id/11597573

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2001-10-12
pubmed:abstractText
To investigate the domains of the parathyroid hormone (PTH) receptor required for regulation by G protein-coupled receptor kinases (GRKs), we created mutant PTH receptors lacking potential GRK-phosphorylation sites. Mutant #1 was truncated at amino acid 544 and, therefore, lacked nine hydroxyl group-containing amino acids at the C-terminus. In mutant #2, we replaced threonines 392 and 399 in the third intracellular loop with glycines. Co-transfection of HEK293 cells with the wild-type receptor and either GRK2, GRK3, or GRK5 inhibited PTH-induced cyclic (cAMP) generation; co-transfection of GRK4 or GRK6 had no effect on PTH receptor responsiveness. GRK2-mediated inhibition of PTH receptor signaling was associated with enhanced phosphorylation receptor proteins. Co-expression of GRK2 similarly reduced PTH-induced cAMP generation by the wild-type receptor and mutant #1, and caused phosphorylation of receptor proteins to a similar extent. Co-expression of GRK2 had little effect on PTH-induced cAMP generation by mutant #2 but enhanced agonist-induced phosphorylation of mutant #2 compared with that of either the wild-type receptor or mutant #1. Enhanced phosphorylation of mutant #2 was associated with a reduction in agonist-induced internalization of mutant #2 compared with the wild-type receptor. Thus, phosphorylation of mutant #2 failed to cause receptor desensitization and inhibited receptor internalization. These data are consistent with the notion that: (a) GRKs contribute to regulating PTH receptor responsiveness, and (b) domains in the third intracellular loop are not required for agonist-induced phosphorylation of PTH receptors, but are critical for both agonist-induced internalization of PTH receptors and GRK2-mediated regulation of PTH receptor signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
62
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1047-58
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:11597573-Amino Acid Substitution, pubmed-meshheading:11597573-Animals, pubmed-meshheading:11597573-Cells, Cultured, pubmed-meshheading:11597573-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:11597573-Endocytosis, pubmed-meshheading:11597573-G-Protein-Coupled Receptor Kinase 3, pubmed-meshheading:11597573-Glycine, pubmed-meshheading:11597573-Humans, pubmed-meshheading:11597573-Iodine Radioisotopes, pubmed-meshheading:11597573-Mutation, pubmed-meshheading:11597573-Parathyroid Hormone, pubmed-meshheading:11597573-Phosphorylation, pubmed-meshheading:11597573-Protein Structure, Tertiary, pubmed-meshheading:11597573-Radioligand Assay, pubmed-meshheading:11597573-Rats, pubmed-meshheading:11597573-Receptors, Parathyroid Hormone, pubmed-meshheading:11597573-Threonine, pubmed-meshheading:11597573-beta-Adrenergic Receptor Kinases
pubmed:year
2001
pubmed:articleTitle
Domains of the parathyroid hormone (PTH) receptor required for regulation by G protein-coupled receptor kinases (GRKs).
pubmed:affiliation
Division of Nephrology, Department of Medicine, Duke University and Durham VA Medical Centers, Box 3014, Durham, NC 27710, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't