The activities of the pleiotropic cytokine LIF are mediated through a high-affinity heterodimeric receptor complex consisting of two membrane glycoproteins: an alpha subunit (LIF R alpha, also known as LIF R and CD118) that binds LIF with low affinity and the 130 kDa (gp130) subunit that does not bind LIF by itself, but is required for high-affinity binding of LIF by the complex. The gp130 subunit was first described as the signal transducing subunit of the high-affinity IL-6 receptor complex. Besides LIF, the high-affinity heterodimeric LIF receptor complex has been shown to mediate the activities of oncostatin M (OSM), cardiotrophin-1 and ciliary neurotrophic factor (CNTF).
Human LIF R alpha cDNA encodes a 1097 amino acid (aa) residue precursor type I membrane protein with a 44 aa residue signal peptide, a 789 aa residue extracellular domain, a 26 aa residue transmembrane domain, and a 238 aa residue cytoplasmic domain. LIF R alpha is a member of the cytokine receptor family and has extensive homology to gp130. The extracellular domain of LIF R alpha has two cytokine receptor domains and three fibronectin type III repeats. In mouse, mRNAs encoding a soluble LIF R alpha and lacking transmembrane and intracellular domains, have been isolated. Soluble LIF R alpha has been shown to bind LIF and has LIF antagonistic activity.
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