Ligand-specific conformational change of the G-protein–coupled receptor ALX/FPR2 determines proresolving functional responses
National Academy of Sciences, 2013
academicJournal
Zugriff:
Inflammation is a crucial host defense response but can cause chronic disease if unregulated. Several endogenous anti-inflammatory and proresolving circuits balance and modulate inflammation, including a mechanism centered on the formyl peptide receptor (FPR) family. One receptor, ALX/FPR2, recognizes both proinflammatory and proresolving signals. We have investigated this unusual molecular mechanism finding that anti-inflammatory, but not proinflammatory signals, activate homodimers of this receptor. This triggers intracellular changes culminating in the release of anti-inflammatory mediators such as IL-10. Heterodimers of ALX with other FPR receptors can transduce proapoptotic signals. These results explain how both the development and resolution of inflammation may be integrated by the same receptor system and show how drugs can be developed that have only anti-inflammatory effects.
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Ligand-specific conformational change of the G-protein–coupled receptor ALX/FPR2 determines proresolving functional responses
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Autor/in / Beteiligte Person: | Cooray, Sadani N. ; Gobbetti, Thomas ; Montero-Melendez, Trinidad ; McArthur, Simon ; Thompson, Dawn ; Clark, Adrian J. L. ; Flower, Roderick J. ; Perretti, Mauro |
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Veröffentlichung: | National Academy of Sciences, 2013 |
Medientyp: | academicJournal |
DOI: | 10.1073/pnas.1308253110 |
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