Leukemia Inhibitory Factor Receptor alpha (LIF R-alpha), also known as LIFR beta and CD118, is a 190kD type I transmembrane protein in the Interleukin-6 receptor family. Members of this family mediate the biological effects of Cardiotrophin-1, CLC, CNTF, IL-6, IL-11, IL-27, and Oncostatin M. Mature mouse LIF R-alpha consists of a 785aa extracellular domain (ECD) with two cytokine receptor homology domains, one WSxWS motif, and three fibronectin type III repeats, followed by a 25aa transmembrane segment and a 239aa cytoplasmic domain. Within the ECD, mouse LIF R-alpha shares 73% and 90% aa sequence identity with human and rat LIF R-alpha, respectively. Alternative splicing generates a 90kD soluble form of the mouse LIF R-alpha ECD. LIF R-alpha binds the pleiotropic cytokine LIF with low affinity, and the soluble isoform retains LIF-binding activity. Binding affinity is increased by the ligand-induced association of LIF R-alpha with the signal transducing subunit gp130. The LIF R-alpha/gp130 receptor complex also transduces Oncostatin M signals, although LIF R-alpha alone does not interact with Oncostatin M. gp130 associates with different ligand-specific receptors to form signaling receptor complexes for the other IL-6 family ligands. The CNTF receptor is a ternary complex that contains CNTF R-alpha and gp130 as well as LIF R-alpha. LIF R-alpha is widely expressed, and LIF induces the proliferation, differentiation, and activation of cells in many tissues. In particular, LIF R-alpha plays an important role in several aspects of early pregnancy such as blastocyst implantation in the uterus.
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