How does MIF mediate signal transduction through its receptor?
From a structural perspective, the signaling properties of a CD74 homotrimer are not apparent. The cytosolic domain of CD74 is only 29-46 aa in length – depending on which of two alternative, in-phase initiation codons are translated 42, and it lacks homology with the catalytic domains of tyrosine or serine/threonine kinases, or with domains that might interact with non-receptor tyrosine kinases, or nucleotide binding proteins. The intracytoplasmic portion of CD74 is known to undergo phosphorylation (Ser6, Ser8), in a protein-kinase dependent manner, but evidence supporting ligand activation in this process has not been reported 54. It nevertheless is noteworthy that recent studies have identified an accessory role for CD74 in T cell stimulation, and by a function that requires a chondroitin-sulphate-dependent interaction between CD74 and CD44 33, 34. CD44 is a widely-expressed, polymorphic transmembrane protein with known tyrosine kinase activation properties 55. Recent evidence in su
