The leukemia inhibitory factor (LIF) 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, glycoprotein 130 (IL6ST, 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.[5]
Leukemia inhibitory factor receptor has been shown to interact with glycoprotein 130.[6][7]
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 (June 2002). "A functional role of the membrane-proximal extracellular domains of the signal transducer gp130 in heterodimerization with the leukemia inhibitory factor receptor". European Journal of Biochemistry. 269 (11): 2716–26. doi:10.1046/j.1432-1033.2002.02941.x. PMID12047380.
Tomida M (May 2000). "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". Leukemia & Lymphoma. 37 (5–6): 517–25. doi:10.3109/10428190009058503. PMID11042511. S2CID22834354.
Gearing DP, Bruce AG (January 1992). "Oncostatin M binds the high-affinity leukemia inhibitory factor receptor". The New Biologist. 4 (1): 61–5. PMID1536831.
Gearing DP, Comeau MR, Friend DJ, Gimpel SD, Thut CJ, McGourty J, Brasher KK, King JA, Gillis S, Mosley B (March 1992). "The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor". Science. 255 (5050): 1434–7. Bibcode:1992Sci...255.1434G. doi:10.1126/science.1542794. PMID1542794.
Gearing DP, Druck T, Huebner K, Overhauser J, Gilbert DJ, Copeland NG, Jenkins NA (October 1993). "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". Genomics. 18 (1): 148–50. doi:10.1006/geno.1993.1441. PMID8276403.
Kojima K, Kanzaki H, Iwai M, Hatayama H, Fujimoto M, Narukawa S, Higuchi T, Kaneko Y, Mori T, Fujita J (July 1995). "Expression of leukaemia inhibitory factor (LIF) receptor in human placenta: a possible role for LIF in the growth and differentiation of trophoblasts". Human Reproduction. 10 (7): 1907–11. doi:10.1093/oxfordjournals.humrep.a136205. PMID8583009.
Tomida M, Gotoh O (July 1996). "Structure of the gene encoding the human differentiation-stimulating factor/leukemia inhibitory factor receptor". Journal of Biochemistry. 120 (1): 201–5. doi:10.1093/oxfordjournals.jbchem.a021386. PMID8864865.
Tanaka M, Hara T, Copeland NG, Gilbert DJ, Jenkins NA, Miyajima A (February 1999). "Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular cloning of the mouse OSM receptor beta subunit". Blood. 93 (3): 804–15. doi:10.1182/blood.V93.3.804. PMID9920829. S2CID39078004.
Knight DA, Lydell CP, Zhou D, Weir TD, Robert Schellenberg R, Bai TR (April 1999). "Leukemia inhibitory factor (LIF) and LIF receptor in human lung. Distribution and regulation of LIF release". American Journal of Respiratory Cell and Molecular Biology. 20 (4): 834–41. doi:10.1165/ajrcmb.20.4.3429. PMID10101017.
Bamberger AM, Schulte HM, Wullbrand A, Jung R, Beil FU, Bamberger CM (April 2000). "Expression of leukemia inhibitory factor (LIF) and LIF receptor (LIF-R) in the human adrenal cortex: implications for steroidogenesis". Molecular and Cellular Endocrinology. 162 (1–2): 145–9. doi:10.1016/S0303-7207(00)00200-8. PMID10854707. S2CID24089439.