Figure 2.

Signaling by exogenous MIF. MIF can induce signaling cascades through its receptors CD74, CXCR2, and CXCR4. These pathways underlie MIF’s biological functions, e.g., leukocytic integrin activation, cell proliferation, and anti-apoptosis, induction of pro-inflammatory gene expression. The detailed molecular mechanism underlying MIF’s arrest function through its receptors CXCR2 and CXCR4 is still unexplored. Three main steps in GPCR-mediated integrin activation can be distinguished, i.e., PLC-mediated calcium mobilization, activation of small GTPases and recruitment of actin-binding proteins linking the integrin to the actin cytoskeleton. PIP2, phosphatidylinosytol 4,5-biphosphate; PLC, phospholipase C; IP3, inosytol 1,4,5-triphosphate; DAG, diacylglycerol; Ca²⁺, calcium; ER, endoplasmic reticulum; GDP, guanosine diphosphate; GTP, guanosine triphosphate; guanine nucleotide exchange factor; PLA2, phospholipase A2; ERK, extracellular signal-related kinase; PI3K, phosphatidylinositol 3-kinase; NF-κB, nuclear factor-κB; BAD, BCL2-associated agonist of cell death; FOXO3A, forkhead box O3a; COX-2, cytochrome C oxidase subunit 2; JNK, c-Jun N-terminal kinase; AP1 (c-Jun), activator protein-1.