Linked Life Data

12672058

Source:http://linkedlifedata.com/resource/pubmed/id/12672058

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-4-2
pubmed:abstractText
The anaphylatoxic peptide C3a is a pro-inflammatory mediator generated during complement activation, whose specific G protein coupled receptor is expressed on granulocytes, monocytes, mast cells, activated lymphocytes, and in the nervous tissue. We have generated RBL-2H3 cell clones stably expressing mutants of the human C3a-receptor (C3aR) with combined alanine (Ala) substitutions of ten C-terminal serine (Ser) or threonine (Thr) residues, which may represent putative phosphorylation sites to characterize their role in ligand-induced C3aR internalization and signaling. Ser475/479 and Thr480/481 as well as Ser449 seemed not to be involved in ligand-induced receptor internalization. Either directly or by a conformational change they even "inhibit" C3aR internalization. In contrast, mutants with Ala substitutions at Ser465/470 and Thr463/466 were poorly internalized, and Thr463 seemed to be the most important C-terminal Thr or Ser residue directly effecting receptor internalization. However, it is likely that other C3aR regions additionally participate in this negative feed-back mechanism since even mutants with multiple Ala substitutions still internalized to a limited degree. Interestingly, in a mutant with a single exchange of Ser449 to Ala, the signal transduction assessed by a Ca(2+) assay and [(35)S]GTP gamma S-binding on HEK cells transiently co-transfected with G-alpha 16 or G-alpha O, respectively, was severely impaired, indicating that this residue of C3aR is involved in G protein coupling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/G protein alpha 16, http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha Subunits, http://linkedlifedata.com/resource/pubmed/chemical/GTP-Binding Protein alpha..., http://linkedlifedata.com/resource/pubmed/chemical/Heterotrimeric GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Complement, http://linkedlifedata.com/resource/pubmed/chemical/Serine, http://linkedlifedata.com/resource/pubmed/chemical/Threonine, http://linkedlifedata.com/resource/pubmed/chemical/complement C3a receptor, http://linkedlifedata.com/resource/pubmed/chemical/olfactory G protein subunit alpha...
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0014-2980
pubmed:author
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
920-7
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Structure-function studies of the C3a-receptor: C-terminal serine and threonine residues which influence receptor internalization and signaling.
pubmed:affiliation
Department of Medical Microbiology, Medical School Hannover, Hannover, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't