Linked Life Data

10029516

Source:http://linkedlifedata.com/resource/pubmed/id/10029516

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1999-3-16
pubmed:abstractText
The human N-formyl peptide receptor (FPR) is representative of a growing family of G protein-coupled receptors (GPCR) that respond to chemokines and chemoattractants. Despite the importance of this receptor class to immune function, relatively little is known about the molecular mechanisms involved in their activation. To reveal steps required for the activation of GPCR receptors, we utilized mutants of the FPR which have previously been shown to be incapable of binding and activating G proteins. For this study, the FPR mutants were expressed in human myeloid U937 cells and characterized for functions in addition to G protein coupling, such as receptor phosphorylation and ligand-induced receptor internalization. The results demonstrated that one of the mutants, R123G, though being unable to activate G protein, was capable of undergoing ligand-induced phosphorylation as well as internalization. Receptor internalization was monitored by following the fate of the ligand as well as by directly monitoring the fate of the receptor. The results with the R123G mutant were in contrast to those obtained for mutants D71A and R309G/E310A/R311G which, though being expressed at the cell surface and binding ligand, were incapable of being phosphorylated or internalized upon agonist stimulation. These results suggest that following ligand binding at least two "steps" are required for full activation of the wild-type FPR. That these observations may be of more general importance in GPCR-mediated signaling is suggested by the highly conserved nature of the mutants studied: D71, R123, and the site represented by amino acids 309-311 are very highly conserved throughout the entire superfamily of G protein-coupled receptors. Models of receptor activation based on the observed results are discussed.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
23
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2240-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10029516-Animals, pubmed-meshheading:10029516-Calcium Signaling, pubmed-meshheading:10029516-Cell Line, pubmed-meshheading:10029516-Fibroblasts, pubmed-meshheading:10029516-Flow Cytometry, pubmed-meshheading:10029516-GTP-Binding Proteins, pubmed-meshheading:10029516-Humans, pubmed-meshheading:10029516-Ligands, pubmed-meshheading:10029516-Mice, pubmed-meshheading:10029516-Mice, Inbred C57BL, pubmed-meshheading:10029516-Models, Biological, pubmed-meshheading:10029516-Models, Molecular, pubmed-meshheading:10029516-Mutagenesis, Site-Directed, pubmed-meshheading:10029516-N-Formylmethionine Leucyl-Phenylalanine, pubmed-meshheading:10029516-Phosphorylation, pubmed-meshheading:10029516-Receptors, Formyl Peptide, pubmed-meshheading:10029516-Receptors, Immunologic, pubmed-meshheading:10029516-Receptors, Peptide, pubmed-meshheading:10029516-U937 Cells
pubmed:year
1999
pubmed:articleTitle
Multiple activation steps of the N-formyl peptide receptor.
pubmed:affiliation
Department of Cell Biology and Physiology, University of New Mexico Health Science Center, Albuquerque 87131, USA. eprossnitz@salud.unm.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't