Distinct Signaling Cascades Elicited by Different Formyl Peptide Receptor 2 (FPR2) Agonists.docVIP

Int. J. Mol. Sci. 2013, 14, 7193-7230; doi:10.3390/ijmOPEN ACCESS International Journal of Molecular Sciences ISSN 1422-0067 /journal/ijms Review Distinct Signaling Cascades Elicited by Different Formyl Peptide Receptor 2 (FPR2) Agonists Fabio Cattaneo, Melania Parisi and Rosario Ammendola * Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Naples, Italy; E-Mails: fabio.cattaneo@unina.it (F.C.); parisi_me@libero.it (M.P.) * Author to whom correspondence should be addressed; E-Mail: rosario.ammendola@unina.it; Tel.: +39-081-746-3145; Fax: +39-081-746-4359. Received: 31 January 2013; in revised form: 13 March 2013 / Accepted: 15 March 2013 / Published: 2 April 2013 Abstract: The formyl peptide receptor 2 (FPR2) is a remarkably versatile transmembrane protein belonging to the G-protein coupled receptor (GPCR) family. FPR2 is activated by an array of ligands, which include structurally unrelated lipids and peptide/proteins agonists, resulting in different intracellular responses in a ligand-specific fashion. In addition to the anti-inflammatory lipid, lipoxin A4, several other endogenous agonists also bind FPR2, including serum amyloid A, glucocorticoid-induced annexin 1, urokinase and its receptor, suggesting that the activation of FPR2 may result in potent pro- or anti-inflammatory responses. Other endogenous ligands, also present in biological samples, include resolvins, amyloidogenic proteins, such as beta amyloid (Aβ)-42 and prion protein (Prp)106–126, the neuroprotective peptide, humanin, antibacterial peptides, annexin 1-derived peptides, chemokine variants, the neuropeptides, vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP)-27, and mitochondrial peptides. Upon activation, intracellular domains of FPR2 mediate signaling to G-proteins, which trigger se