The leukemia inhibitory factor is a polyfunctional cytokine that affects the differentiation, survival, and proliferation of a wide variety of cells in the adult and the embryo. LIF action appears to be mediated through a high-affinity receptor complex composed of a low-affinity LIF binding chain (LIF receptor) and a high-affinity converter subunit, gp130. Both LIFR and gp130 are members of a family of cytokine receptors that includes components of the receptors for the majority of hematopoietic cytokines and for cytokines that affect other systems, including the ciliary neurotrophic factor, growth hormone and prolactin.
LIFR has also been identified as a breast cancer metastasis suppressor that functions through the HIPPO-YAP pathway. LIFR is down regulated in a number of breast carcinomas and may serve a prognostic tool.
^Timmermann A, Küster A, Kurth I, Heinrich PC, Müller-Newen G (Jun 2002). "A functional role of the membrane-proximal extracellular domains of the signal transducer gp130 in heterodimerization with the leukemia inhibitory factor receptor". Eur. J. Biochem. (Germany) 269 (11): 2716–26. doi:10.1046/j.1432-1033.2002.02941.x. ISSN0014-2956. PMID12047380.
^Mosley, B; De Imus C; Friend D; Boiani N; Thoma B; Park L S; Cosman D (Dec 1996). "Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation". J. Biol. Chem. (UNITED STATES) 271 (51): 32635–43. doi:10.1074/jbc.271.51.32635. ISSN0021-9258. PMID8999038.
Tomida M (2003). "Structural and functional studies on the leukemia inhibitory factor receptor (LIF-R): gene and soluble form of LIF-R, and cytoplasmic domain of LIF-R required for differentiation and growth arrest of myeloid leukemic cells.". Leuk. Lymphoma37 (5–6): 517–25. doi:10.3109/10428190009058503. PMID11042511.
Gearing DP, Bruce AG (1992). "Oncostatin M binds the high-affinity leukemia inhibitory factor receptor". New Biol.4 (1): 61–5. PMID1536831.
Gearing DP, Comeau MR, Friend DJ, et al. (1992). "The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor". Science255 (5050): 1434–7. doi:10.1126/science.1542794. PMID1542794.
Boulton TG, Stahl N, Yancopoulos GD (1994). "Ciliary neurotrophic factor/leukemia inhibitory factor/interleukin 6/oncostatin M family of cytokines induces tyrosine phosphorylation of a common set of proteins overlapping those induced by other cytokines and growth factors". J. Biol. Chem.269 (15): 11648–55. PMID7512571.
Gearing DP, Druck T, Huebner K, et al. (1994). "The leukemia inhibitory factor receptor (LIFR) gene is located within a cluster of cytokine receptor loci on mouse chromosome 15 and human chromosome 5p12-p13". Genomics18 (1): 148–50. doi:10.1006/geno.1993.1441. PMID8276403.
Sharkey AM, Dellow K, Blayney M, et al. (1996). "Stage-specific expression of cytokine and receptor messenger ribonucleic acids in human preimplantation embryos". Biol. Reprod.53 (4): 974–81. doi:10.1095/biolreprod53.4.974. PMID8547494.
Kojima K, Kanzaki H, Iwai M, et al. (1996). "Expression of leukaemia inhibitory factor (LIF) receptor in human placenta: a possible role for LIF in the growth and differentiation of trophoblasts". Hum. Reprod.10 (7): 1907–11. PMID8583009.
Wang Z, Melmed S (1997). "Identification of an upstream enhancer within a functional promoter of the human leukemia inhibitory factor receptor gene and its alternative promoter usage". J. Biol. Chem.272 (44): 27957–65. doi:10.1074/jbc.272.44.27957. PMID9346946.
Tanaka M, Hara T, Copeland NG, et al. (1999). "Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular cloning of the mouse OSM receptor beta subunit". Blood93 (3): 804–15. PMID9920829.
Knight DA, Lydell CP, Zhou D, et al. (1999). "Leukemia inhibitory factor (LIF) and LIF receptor in human lung. Distribution and regulation of LIF release". Am. J. Respir. Cell Mol. Biol.20 (4): 834–41. doi:10.1165/ajrcmb.20.4.3429. PMID10101017.
Bartoe JL, Nathanson NM (2000). "Differential regulation of leukemia inhibitory factor-stimulated neuronal gene expression by protein phosphatases SHP-1 and SHP-2 through mitogen-activated protein kinase-dependent and -independent pathways". J. Neurochem.74 (5): 2021–32. doi:10.1046/j.1471-4159.2000.0742021.x. PMID10800945.
Bamberger AM, Schulte HM, Wullbrand A, et al. (2000). "Expression of leukemia inhibitory factor (LIF) and LIF receptor (LIF-R) in the human adrenal cortex: implications for steroidogenesis". Mol. Cell. Endocrinol.162 (1–2): 145–9. doi:10.1016/S0303-7207(00)00200-8. PMID10854707.
Blanchard F, Duplomb L, Wang Y, et al. (2000). "Stimulation of leukemia inhibitory factor receptor degradation by extracellular signal-regulated kinase". J. Biol. Chem.275 (37): 28793–801. doi:10.1074/jbc.M003986200. PMID10858440.