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• W1890667195 endingPage "4511" @default.
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• W1890667195 abstract "Macrophage migration-inhibitory factor (MIF) is a pleiotropic cytokine with chemokine-like functions and is a mediator in numerous inflammatory conditions. Depending on the context, MIF signals through 1 or more of its receptors cluster of differentiation (CD)74, CXC-motif chemokine receptor (CXCR)2, and CXCR4. In addition, heteromeric receptor complexes have been identified. We characterized the atypical chemokine receptor CXCR7 as a novel receptor for MIF. MIF promoted human CXCR7 internalization up to 40%, peaking at 50-400 nM and 30 min, but CXCR7 internalization by MIF was not dependent on CXCR4. Yet, by coimmunoprecipitation, fluorescence microscopy, and a proximity ligation assay, CXCR7 was found to engage in MIF receptor complexes with CXCR4 and CD74, both after ectopic overexpression and in endogenous conditions in a human B-cell line. Receptor competition binding and coimmunoprecipitation studies combined with sulfo-SBED-biotintransfer provided evidence for a direct interaction between MIF and CXCR7. Finally, we demonstrated MIF/CXCR7-mediated functional responses. Blockade of CXCR7 suppressed MIF-mediated ERK- and zeta-chain-associated protein kinase (ZAP)-70 activation (from 2.1- to 1.2-fold and from 2.5- to 1.6-fold, respectively) and fully abrogated primary murine B-cell chemotaxis triggered by MIF, but not by CXCL12. B cells from Cxcr7-/- mice exhibited an ablated transmigration response to MIF, indicating that CXCR7 is essential for MIF-promoted B-cell migration. Our findings provide biochemical and functional evidence that MIF is an alternative ligand of CXCR7 and suggest a functional role of the MIF-CXCR7 axis in B-lymphocyte migration.—Alampour-Rajabi, S., El Bounkari, O., Rot, A., Müller-Newen, G., Bachelerie, F., Gawaz, M., Weber, C., Schober, A., Bernhagen, J. MIF interacts with CXCR7 to promote receptor internalization, ERK1/2 and ZAP-70 signaling, and lymphocyte chemotaxis. FASEB J. 29, 4497-4511 (2015). www.fasebj.org" @default.
• W1890667195 created "2016-06-24" @default.
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• W1890667195 date "2015-07-02" @default.
• W1890667195 modified "2023-10-18" @default.
• W1890667195 title "MIF interacts with CXCR7 to promote receptor internalization, ERK1/2 and ZAP‐70 signaling, and lymphocyte chemotaxis" @default.
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• W1890667195 doi "https://doi.org/10.1096/fj.15-273904" @default.
• W1890667195 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26139098" @default.
• W1890667195 hasPublicationYear "2015" @default.
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