Leukemia inhibitory factor receptor explained

LIFR also known as CD118 (Cluster of Differentiation 118), is a subunit of a receptor for leukemia inhibitory factor.

Function

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.^[1]

Interactions

Leukemia inhibitory factor receptor has been shown to interact with glycoprotein 130.^{[2] [3]}

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.

See also

• Cluster of differentiation

Further reading

• Tomida M . 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 . May 2000 . 11042511 . 10.3109/10428190009058503 . 22834354 .
• Lass A, Weiser W, Munafo A, Loumaye E . Leukemia inhibitory factor in human reproduction . Fertility and Sterility . 76 . 6 . 1091–6 . December 2001 . 11730732 . 10.1016/S0015-0282(01)02878-3 . free .
• Gearing DP, Bruce AG . Oncostatin M binds the high-affinity leukemia inhibitory factor receptor . The New Biologist . 4 . 1 . 61–5 . January 1992 . 1536831 .
• Gearing DP, Comeau MR, Friend DJ, Gimpel SD, Thut CJ, McGourty J, Brasher KK, King JA, Gillis S, Mosley B . The IL-6 signal transducer, gp130: an oncostatin M receptor and affinity converter for the LIF receptor . Science . 255 . 5050 . 1434–7 . March 1992 . 1542794 . 10.1126/science.1542794 . 1992Sci...255.1434G .
• Gearing DP, Thut CJ, VandeBos T, Gimpel SD, Delaney PB, King J, Price V, Cosman D, Beckmann MP . Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130 . The EMBO Journal . 10 . 10 . 2839–48 . October 1991 . 1915266 . 452994 . 10.1002/j.1460-2075.1991.tb07833.x.
• Boulton TG, Stahl N, Yancopoulos GD . 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 . April 1994 . 10.1016/S0021-9258(19)78174-5 . 7512571 . free .
• Schiemann WP, Graves LM, Baumann H, Morella KK, Gearing DP, Nielsen MD, Krebs EG, Nathanson NM . Phosphorylation of the human leukemia inhibitory factor (LIF) receptor by mitogen-activated protein kinase and the regulation of LIF receptor function by heterologous receptor activation . Proceedings of the National Academy of Sciences of the United States of America . 92 . 12 . 5361–5 . June 1995 . 7777512 . 41694 . 10.1073/pnas.92.12.5361 . 1995PNAS...92.5361S . free .
• Gearing DP, Druck T, Huebner K, Overhauser J, Gilbert DJ, Copeland NG, Jenkins NA . 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 . October 1993 . 8276403 . 10.1006/geno.1993.1441 .
• Sharkey AM, Dellow K, Blayney M, Macnamee M, Charnock-Jones S, Smith SK . Stage-specific expression of cytokine and receptor messenger ribonucleic acids in human preimplantation embryos . Biology of Reproduction . 53 . 4 . 974–81 . October 1995 . 8547494 . 10.1095/biolreprod53.4.974 . free .
• Kojima K, Kanzaki H, Iwai M, Hatayama H, Fujimoto M, Narukawa S, Higuchi T, Kaneko Y, Mori T, Fujita J . 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 . July 1995 . 8583009 . 10.1093/oxfordjournals.humrep.a136205.
• Tomida M, Gotoh O . Structure of the gene encoding the human differentiation-stimulating factor/leukemia inhibitory factor receptor . Journal of Biochemistry . 120 . 1 . 201–5 . July 1996 . 8864865 . 10.1093/oxfordjournals.jbchem.a021386 .
• Wang Z, Melmed S . 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 . October 1997 . 9346946 . 10.1074/jbc.272.44.27957 . free .
• Tanaka M, Hara T, Copeland NG, Gilbert DJ, Jenkins NA, Miyajima A . Reconstitution of the functional mouse oncostatin M (OSM) receptor: molecular cloning of the mouse OSM receptor beta subunit . Blood . 93 . 3 . 804–15 . February 1999 . 9920829 . 10.1182/blood.V93.3.804. 39078004 .
• Knight DA, Lydell CP, Zhou D, Weir TD, Robert Schellenberg R, Bai TR . 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 . April 1999 . 10101017 . 10.1165/ajrcmb.20.4.3429 .
• Kakizawa T, Miyamoto T, Ichikawa K, Kaneko A, Suzuki S, Hara M, Nagasawa T, Takeda T, Mori JI, Kumagai M, Hashizume K . Functional interaction between Oct-1 and retinoid X receptor . The Journal of Biological Chemistry . 274 . 27 . 19103–8 . July 1999 . 10383413 . 10.1074/jbc.274.27.19103 . free .
• Bartoe JL, Nathanson NM . 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 . May 2000 . 10800945 . 10.1046/j.1471-4159.2000.0742021.x . 23296203 . free .
• Bamberger AM, Schulte HM, Wullbrand A, Jung R, Beil FU, Bamberger CM . 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 . April 2000 . 10854707 . 10.1016/S0303-7207(00)00200-8 . 24089439 .
• Blanchard F, Duplomb L, Wang Y, Robledo O, Kinzie E, Pitard V, Godard A, Jacques Y, Baumann H . Stimulation of leukemia inhibitory factor receptor degradation by extracellular signal-regulated kinase . The Journal of Biological Chemistry . 275 . 37 . 28793–801 . September 2000 . 10858440 . 10.1074/jbc.M003986200 . free .
• Plun-Favreau H, Elson G, Chabbert M, Froger J, deLapeyrière O, Lelièvre E, Guillet C, Hermann J, Gauchat JF, Gascan H, Chevalier S . The ciliary neurotrophic factor receptor alpha component induces the secretion of and is required for functional responses to cardiotrophin-like cytokine . The EMBO Journal . 20 . 7 . 1692–703 . April 2001 . 11285233 . 145510 . 10.1093/emboj/20.7.1692 .

Notes and References

1. Web site: Entrez Gene: LIFR leukemia inhibitory factor receptor alpha.
2. Timmermann A, Küster A, Kurth I, Heinrich PC, Müller-Newen G . 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 . June 2002 . 12047380 . 10.1046/j.1432-1033.2002.02941.x .
3. Mosley B, De Imus C, Friend D, Boiani N, Thoma B, Park LS, Cosman D . 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 . December 1996 . 8999038 . 10.1074/jbc.271.51.32635 . free .