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A functional heteromeric MIF receptor formed by CD74 and CXCR4

2009; Wiley; Volume: 583; Issue: 17 Linguagem: Inglês

10.1016/j.febslet.2009.07.058

1873-3468

Verena Schwartz, Hongqi Lue, Sandra Kraemer, Joanna Korbiel, Regina M. Krohn, Kim Ohl, Richard Bucala, Christian Weber, Jürgen Bernhagen,

Macrophage Migration Inhibitory Factor

MIF is a chemokine-like inflammatory mediator that triggers leukocyte recruitment by binding to CXCR2 and CXCR4. MIF also interacts with CD74/invariant chain, a single-pass membrane-receptor. We identified complexes between CD74 and CXCR2 with a role in leukocyte recruitment. It is unknown whether CD74 also binds to CXCR4. We demonstrate that CD74/CXCR4 complexes formed when CD74 was expressed with CXCR4 in HEK293 cells. Expression of CD74-variants lacking an ER-retention signal showed CD74/CXCR4 complexes at the cell surface. Importantly, endogenous CD74/CXCR4 complexes were isolated by co-immunoprecipitation from monocytes. Finally, MIF-stimulated CD74-dependent AKT activation was blocked by anti-CXCR4 and anti-CD74 antibodies and AMD3100, whereas CXCL12-stimulated AKT activation was not reduced by anti-CD74. Thus, CD74 forms functional complexes with CXCR4 that mediate MIF-specific signaling.