Recombinant Mouse MIF Protein

MIF (or macrophage migration inhibitory factor) was the first lymphokine/cytokine to be recognized in the pregenomics era (1, 2). Regardless, it is one of the least understood of all inflammatory mediators (1, 3). Mouse MIF is a 12.5 kDa, 115 amino acid (aa) nonglycosylated polypeptide that is synthesized without a signal sequence (4-7). Secretion occurs nonclassically via an ABCA1 transporter (6). The initiating Met is removed, leaving Pro as the first amino acid. The molecule consists of two alpha-helices and six beta-strands, four of which form a beta-sheet. The two remaining beta-strands interact with other MIF molecules, creating a trimer (2, 8). Structure-function studies suggests MIF is bifunctional with segregated topology. The N- and C-termini mediate enzyme activity (in theory). Phenylpyruvate tautomerase activity (enol- to-keto) has been demonstrated and is dependent upon Pro at position #1 (9). Amino acids 3-23 have also been shown to be reminescent of a GST glutathione-binding domain (10). MIF has proinflammatory cytokine activity centered on aa’s 49-65. On fibroblasts, MIF induces, IL-1, IL-8 and MMP expression; on macrophages, MIF stimulates, NO production and TNF-alpha release following IFN-gamma activation (11, 12). Mouse MIF apparently acts through CD74 and CD44, likely in some form of trimeric interaction (13, 14). Mouse MIF is active on human cells, while human MIF is active on mouse cells (12). Mouse MIF is 99%, 84%, 90%, and 90% aa identical to rat, porcine, bovine and human MIF, respectively.