QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: mol.107.040915v1 73/5/1362    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Chakera, A. Articles by Greaves, D. R. Search for Related Content PubMed PubMed Citation Articles by Chakera, A. Articles by Greaves, D. R.

The Duffy Antigen/Receptor for Chemokines Exists in an Oligomeric Form in Living Cells and Functionally Antagonizes CCR5 Signaling through Hetero-Oligomerization

Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom (A.C., A.E.J., D.R.G.) and the Western Australian Institute for Medical Research and Centre for Medical Research, University of Western Australia, Nedlands, Western Australia, Australia (R.M.S., K.A.E.)

The Duffy antigen/receptor for chemokines (DARC) is an unusual chemokine receptor that binds a large number of inflammatory chemokines of both the CC and CXC families with nanomolar affinity, yet it lacks the ability to signal upon ligand binding. Using bioluminescent resonant energy transfer, we have demonstrated for the first time that DARC exists as a constitutive homo-oligomer in living cells and furthermore that DARC hetero-oligomerizes with the CC chemokine receptor CCR5. DARC-CCR5 interaction impairs chemotaxis and calcium flux through CCR5, whereas internalization of CCR5 in response to ligand binding remains unchanged. These results suggest a novel mechanism by which DARC could modulate inflammatory responses to chemokines in vivo.

Address correspondence to: Dr. David R. Greaves, Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford OX1 3RE, UK. E-mail: david.greaves{at}path.ox.ac.uk