MIF Signal Transduction Initiated by Binding to CD74
By L. Leng, C. Metz, Yan Fang, Jing Xu, S. Donnelly, J. Baugh, T. Delohery, Yibang Chen, R. Mitchell, R. Bucala. Journal of Experimental Medicine, 2003
1,124 citations recorded by the source corpus.
Macrophage migration inhibitory factor (MIF) accounts for one of the first cytokine activities to have been described, and it has emerged recently to be an important regulator of innate and adaptive immunity. MIF is an upstream activator of monocytes/macrophages, and it is centrally involved in the pathogenesis of septic shock, arthritis, and other inflammatory conditions. The protein is encoded by a unique but highly conserved gene, and X-ray crystallography studies have shown MIF to define a new protein fold and structural superfamily. Although recent work has begun to illuminate the signal transduction pathways activated by MIF, the nature of its membrane receptor has not been known. Using expression cloning and functional analysis, we report herein that CD74, a Type II transmembrane protein, is a high-affinity binding protein for MIF. MIF binds to the extracellular domain of CD74, and CD74 is required for MIF-induced activation of the extracellular signal–regulated kinase–1/2 MAP kinase cascade, cell proliferation, and PGE2 production. A recombinant, soluble form of CD74 binds MIF with a dissociation constant of ∼9 × 10−9 K d, as defined by surface plasmon resonance (BIAcore analysis), and soluble CD74 inhibits MIF-mediated extracellular signal–regulated kinase activation in defined cell systems. These data provide a molecular basis for MIF's interaction with target cells and identify it as a natural ligand for CD74, which has been implicated previously in signaling and accessory functions for immune cell activation.
Subfields: Cellular and Molecular Neuroscience, Immunology
View Paper: https://www.semanticscholar.org/paper/044eb4181038a9fe6751f6770a0047d1a4f67251
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Citations in the corpus
- CD44 is the signaling component of the macrophage migration inhibitory factor-CD74 receptor complex. (2006, methodology): “1/V5His-TOPO vector (Invitrogen) (Leng et al., 2003).”
- Cytokines in Sepsis: Potent Immunoregulators and Potential Therapeutic Targets—An Updated View (2013, background): “MIF activates immune cells by binding to CD74 (the cell surface form of the class IIassociated invariant chain), which leads to the recruitment of CD44 into a signaling complex and the downstream initiation of the ERK1/2 MAP kinase pathway [163, 164].”
- Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. (2007, neutral): “As shown in Figure 4F c-ROS is fused to the N-terminal half of CD74, a type II transmembrane protein with high affinity for the MIF immune cytokine (Leng et al., 2003).”
- MIF is a noncognate ligand of CXC chemokine receptors in inflammatory and atherogenic cell recruitment (2007, background): “CD74 (also known as invariant chain) binds MIF on the surface of cells, can mediate activation of extracellular-regulated mitogen-activated protein (ERK-MAP) kinases and associates into a signaling complex with MIF, CD44 and Src-tyrosine kinase”
- Macrophage migration inhibitory factor: a regulator of innate immunity (2003, background): “MIF has been reported to bind to the extracellular domain of CD74 — the cell-surface form of the MHC class-II-associated invariant chai”