NDLI: Annexin A1 Interaction with the FPR2/ALX Receptor IDENTIFICATION OF DISTINCT DOMAINS AND DOWNSTREAM ASSOCIATED SIGNALING

Content Provider	Journal of Biological Chemistry (JBC)
Author	Bena, Stefania Brancaleone, Vincenzo Wang, Ji Ming Perretti, Mauro Flower, Roderick J.
Abstract	Understanding how proresolving agonists selectively activate FPR2/ALX is a crucial step in the clarification of proresolution molecular networks that can be harnessed for the design of novel therapeutics for inflammatory disease. FPR2/ALX, a G protein-coupled receptor belonging to the formyl peptide receptor (FPR) family, conveys the biological functions of a variety of ligands, including the proresolution mediators annexin A1 (AnxA1) and lipoxin A4, as well as the activating and proinflammatory protein serum amyloid A. FPR2/ALX is the focus of intense screening for novel anti-inflammatory therapeutics, and the small molecule compound 43 was identified as a receptor ligand. Here, we used chimeric FPR1 and FPR2/ALX clones (stably transfected in HEK293 cells) to identify the N-terminal region and extracellular loop II as the FPR2/ALX domain required for AnxA1-mediated signaling. Genomic responses were also assessed with domain-specific effects emerging, so the N-terminal region is required for AnxA1 induction of JAG1 and JAM3, whereas it is dispensable for modulation of SGPP2. By comparison, serum amyloid A non-genomic responses were reliant on extracellular loops I and II, whereas the small molecule compound 43 activated extracellular loop I with downstream signaling dependent on transmembrane region II. In desensitization experiments, the N-terminal region was dispensable for AnxA1-induced FPR2/ALX down-regulation in both the homologous and heterologous desensitization modes.
Related Links	http://www.jbc.org/content/287/29/24690.abstract
Ending Page	24697
Starting Page	24690
Page Count	8
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	29
Volume Number	287
DOI	10.1074/jbc.M112.377101
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2012-07-13
Access Restriction	Open
Subject Keyword	7-Helix Receptor Annexin Cell Biology Inflammation Leukocyte Anti-inflammatory Targets Lipoxin A4 Receptor Resolution of Inflammation
Alternative Title	Annexin A1 Interaction with the FPR2/ALX Receptor
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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