CD74 binds MIF

Stable Identifier
R-HSA-5676133
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Macrophage migration inhibitory factor (MIF), one of the first cytokines to be described (George & Vaughan 1962), is an important regulator of innate and adaptive immunity. MIF is an upstream activator of monocytes/macrophages, centrally involved in the pathogenesis of septic shock, arthritis, and other inflammatory conditions (Nishihira 2000, Sanchez-Niño et al. 2013). High-expression Mif alleles are linked to severe rheumatoid arthritis (Morand & Leech 2005). MIF promotes monocyte/macrophage activation and it is required for the optimal expression of TNF-alpha, IL-1, and PGE2 (Calandra & Bucala 1997). MIF-treated macrophages are more phagocytic and better able to destroy intracellular pathogens, such as Leishmania (Rosado & Rodriguez-Sosa 2011). Active MIF is a 37.5 kDa homotrimer.

MIF can bind to CD74 (Leng et al. 2003) and the chemokine receptors CXCR2 and CXCR4 (Bernhagen et al. 2007). Leukocyte recruitment by MIF is mediated by interaction with CXCR2 and CXCR4 (Bernhagen et al. 2007). MIF interaction with CD74 mediates its proproliferative and antiproliferative effects, regulation of B-cell and tumor cell survival, fibrosis and angiogenesis (Starlets et al. 2006). MIF can suppress the immunosuppressive effects of glucocorticoids, inducing a sustained pattern of ERK-1/2 MAP kinase activation (Bach et al. 2009).

MIF is endocytosed to bind the cytosolic protein JAB1 (Schwartz et al. 2012), negatively regulating JAB1-controlled pathways (Kleemann et al. 2000). MIF inhibits JAB1-induced JNK activity, AP-1 activity and JAB1-dependent cell-cycle regulation by stabilizing p27Kip1 protein (Nguyen et al. 2003). Consequently, MIF blocks JAB1-mediated rescue of fibroblasts from growth arrest (Kleemann et al. 2000).

Literature References
PubMed ID Title Journal Year
12782713 MIF signal transduction initiated by binding to CD74

Leng, L, Metz, CN, Fang, Y, Xu, J, Donnelly, S, Baugh, J, Delohery, T, Chen, Y, Mitchell, RA, Bucala, R

J. Exp. Med. 2003
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