Leukemia Inhibitory Factor (LIF) is a pleiotropic glycoprotein originally described to inhibit the proliferation of the murine myeloid leukemic cell line M1, while inducing differentiation into macrophages. Other activities were later identified to LIF, which is known by a variety of synonyms, including DIF, D-factor, DIA, DRF, CNDF, HILDA, HSF-III, and MLPLI. Human LIF exerts its actions through a receptor comprising a 190 kDa LIF-binding α-chain (130 kDa, mouse) and a 130 kDa signal-transducing β-chain (gp130), which is shared with CNTF, OSM, L-6 and IL-11. As such, it is a member of the gp130 family of the cytokine receptor superfamily. LIF receptors have been identified on several cells, including monocytes, liver, placenta and embryonic stem cells. Natural LIF is heavily glycosylated, showing an apparent molecular weight of 32 kDa to 62 kDa, depending on the source, but absence of glycosylation appears not to affect its biological activity. A single gene encodes LIF, which is secreted as a single chain glycoprotein containing 180 amino acids for human or mouse with a conserved disulfide bond. Human and mouse LIF share 78% sequence homology. Human LIF can activate mouse cells, but mouse LIF cannot activate human cells.
