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.[1]
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.
↑Mosley B, De Imus C, Friend D, Boiani N, Thoma B, Park LS, Cosman D (December 1996). "Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation". The Journal of Biological Chemistry. 271 (51): 32635–43. doi:10.1074/jbc.271.51.32635. PMID8999038.
Further reading
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.
Lass A, Weiser W, Munafo A, Loumaye E (December 2001). "Leukemia inhibitory factor in human reproduction". Fertility and Sterility. 76 (6): 1091–6. doi:10.1016/S0015-0282(01)02878-3. PMID11730732.
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. doi:10.1126/science.1542794. PMID1542794.
Boulton TG, Stahl N, Yancopoulos GD (April 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". The Journal of Biological Chemistry. 269 (15): 11648–55. PMID7512571.
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.
Sharkey AM, Dellow K, Blayney M, Macnamee M, Charnock-Jones S, Smith SK (October 1995). "Stage-specific expression of cytokine and receptor messenger ribonucleic acids in human preimplantation embryos". Biology of Reproduction. 53 (4): 974–81. doi:10.1095/biolreprod53.4.974. PMID8547494.
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. 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.
Wang Z, Melmed S (October 1997). "Identification of an upstream enhancer within a functional promoter of the human leukemia inhibitory factor receptor gene and its alternative promoter usage". The Journal of Biological Chemistry. 272 (44): 27957–65. doi:10.1074/jbc.272.44.27957. PMID9346946.
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. PMID9920829.
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.
Kakizawa T, Miyamoto T, Ichikawa K, Kaneko A, Suzuki S, Hara M, Nagasawa T, Takeda T, Mori JI, Kumagai M, Hashizume K (July 1999). "Functional interaction between Oct-1 and retinoid X receptor". The Journal of Biological Chemistry. 274 (27): 19103–8. doi:10.1074/jbc.274.27.19103. PMID10383413.
Bartoe JL, Nathanson NM (May 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". Journal of Neurochemistry. 74 (5): 2021–32. doi:10.1046/j.1471-4159.2000.0742021.x. PMID10800945.
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.
Blanchard F, Duplomb L, Wang Y, Robledo O, Kinzie E, Pitard V, Godard A, Jacques Y, Baumann H (September 2000). "Stimulation of leukemia inhibitory factor receptor degradation by extracellular signal-regulated kinase". The Journal of Biological Chemistry. 275 (37): 28793–801. doi:10.1074/jbc.M003986200. PMID10858440.