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- Title
A functional heteromeric MIF receptor formed by CD74 and CXCR4
- Authors
Schwartz, Verena; Lue, Hongqi; Kraemer, Sandra; Korbiel, Joanna; Krohn, Regina; Ohl, Kim; Bucala, Richard; Weber, Christian; Bernhagen, Jürgen
- Abstract
Abstract: 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. Structured summary: MINT-7234512, MINT-7234528: CD74 (uniprotkb:P04233) physically interacts (MI:0915) with CXCR4 (uniprotkb:P61073) by anti tag coimmunoprecipitation (MI:0007) MINT-7234542: CD74 (uniprotkb:P04233) and CXCR4 (uniprotkb:P61073) physically interact (MI:0915) by anti bait coimmunoprecipitation (MI:0006) MINT-7234499: CXCR4 (uniprotkb:P61073) and CD74 (uniprotkb:P04233) colocalize (MI:0403) by fluorescence microscopy (MI:0416)
- Subjects
INFLAMMATORY mediators; CHEMOKINES; LEUCOCYTES; CELL receptors; CELL communication; CELL membranes; MONOCYTES; GENE expression
- Publication
FEBS Letters, 2009, Vol 583, Issue 17, p2749
- ISSN
0014-5793
- Publication type
Article
- DOI
10.1016/j.febslet.2009.07.058