Atlas of Genetics and Cytogenetics in Oncology and Haematology
LIFR (leukemia inhibitory factor receptor alpha)
| Identity |
| Other names | CD118 |
| FLJ98106 | |
| FLJ99923 | |
| LIF-R | |
| SJS2 | |
| STWS | |
| SWS | |
| HGNC (Hugo) | LIFR |
| LocusID (NCBI) | 3977 |
| Location | 5p13.1 |
| Location_base_pair | Starts at 38475065 and ends at 38556748 bp from pter ( according to hg19-Feb_2009) [Mapping] |
| DNA/RNA |
 | |
| SP: signal peptid CRH1/CRH2: cytokine receptor homology domain Ig: Ig-like domain FNIII: type III fibronectin domain TM: transmembrane domain CD: cytoplasmic domain | |
| Description | At least 20 exons. |
| Transcription | 10258 pb mRNA; 3293 pb open reading frame. |
| Protein |
| Description | 1097 amino acids; 190 kDa. |
| Expression | Chondrocytes; osteoblasts; skin fibroblasts placenta; brain; mixed; muscle; lung; embryonic tissue; uterus; stomach; kidney; ovary; liver; prostate; vascular; thyroid; testis; eye; pancreas; adrenal gland; spleen; thymus; trachea; larynx; connective tissue; ear; ascites; ganglia; nerve; tonsil; heart; adipose tissue; intestine; mouth (not in lymphocytes). |
| Localisation | Cytoplasmic membrane. |
| Function | LIFR (gp190) and gp130 compose an heterodimeric receptor. The addition of ligand LIF enhances the dimer formation and signal transduction involves the activation of the JAK/STAT and MAPK cascades. |
| Homology | With the IL6 cytokine family receptors. LIFR depends of the class I cytokine receptor family. The members of this family contain a conserved domain with ~200 amino acid residues in the amino-terminal half and a WSXWS motif in the carboxy-terminal end. |
| Mutations |
| Note | 14 distinct mutations were identified in 19 families. An identical frameshift insertion (c.653_654insT) was identified in families from the United Arab Emirates, suggesting a founder effect in that region. 12/14 mutations predicted premature termination of translation (Dagoneau et al., 2004; Corona-Rivera et al., 2009). |
 | |
| Implicated in |
| Entity | Stüve-Wiedemann syndrome |
| Note | SWS / SJS2 |
| Disease | Stüve-Wiedemann syndrome is a severe autosomal recessive condition characteried by bowing of the long bones, with cortical thickening, flared metaphyses with coarsened trabecular pattern, camptodactyly, respiratory distress, feeding difficulties, and hyperthermic episodes responsible for early lethality. |
| Entity | ACTH-secreting pituitary adenomas |
| Disease | LIFR was expressed in all ACTH-secreting adenomas and non functioning adenomas. No LIFR mutations were found (Heutling et al., 2004). |
| Entity | Pancreatic carcinoma |
| Disease | Pancreatic carcinoma cells expressed LIF, LIFR and gP130 mRNAs. LIF upregulates LIFR mRNA expression and antisense oligonucleotide of LIFR suppresses cell proliferation. The results may be of potential value in immunotherapy for pancreatic carcinoma (Kamohara et al., 2007). |
| Entity | Neuroblastoma |
| Disease | Growth factors (EGF, FGF) cause a decrease in LIFR levels in neuroblastoma cells that correlated with the activation of extracellular signal-regulated kinase (Erk1/Erk2). The decrease in LIFR is due to an increase in the rate of protein degradation and is blocked by inhibitors of lysosomal degradation (Port et al., 2008). |
| Entity | Glioblastoma multiforme (GBM) |
| Disease | Glioblastoma multiforme (GBM) represents an extremely chemoresistant tumour type. The authors analysed the expression of selected neural and non-neural differentiation markers including LIFR. They found that LIFR expression was associated with chemosensitivity of tumour cells to several chemotherapeutic agents. However, its role in glioma pathogenesis and response to therapy remains to be elucidated. |
| External links |
| Bibliography |
| Congenital bowing of long bones--occurrence in two sisters. |
| Stuve A, Wiedemann HR. |
| Z Kinderheilkd. 1971;111(3):184-92. |
| PMID 5157649 |
| Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130. |
| Gearing DP, Thut CJ, VandeBos T, Gimpel SD, Delaney PB, King J, Price V, Cosman D, Beckmann MP. |
| EMBO J. 1991 Oct;10(10):2839-48. |
| PMID 1915266 |
| 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. |
| Gearing DP, Druck T, Huebner K, Overhauser J, Gilbert DJ, Copeland NG, Jenkins NA. |
| Genomics. 1993 Oct;18(1):148-50. |
| PMID 8276403 |
| Essential function of LIF receptor in motor neurons. |
| Li M, Sendtner M, Smith A. |
| Nature. 1995 Dec 14;378(6558):724-7. |
| PMID 7501019 |
| Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death. |
| Ware CB, Horowitz MC, Renshaw BR, Hunt JS, Liggitt D, Koblar SA, Gliniak BC, McKenna HJ, Papayannopoulou T, Thoma B, et al. |
| Development. 1995 May;121(5):1283-99. |
| PMID 7789261 |
| Structure of the gene encoding the human differentiation-stimulating factor/leukemia inhibitory factor receptor. |
| Tomida M, Gotoh O. |
| J Biochem. 1996 Jul;120(1):201-5. |
| PMID 8864865 |
| Distinct roles for leukemia inhibitory factor receptor alpha-chain and gp130 in cell type-specific signal transduction. |
| Starr R, Novak U, Willson TA, Inglese M, Murphy V, Alexander WS, Metcalf D, Nicola NA, Hilton DJ, Ernst M. |
| J Biol Chem. 1997 Aug 8;272(32):19982-6. |
| PMID 9242667 |
| Clinical homogeneity of the Stuve-Wiedemann syndrome and overlap with the Schwartz-Jampel syndrome type 2. |
| Cormier-Daire V, Superti-Furga A, Munnich A, Lyonnet S, Rustin P, Delezoide AL, De Lonlay P, Giedion A, Maroteaux P, Le Merrer M. |
| Am J Med Genet. 1998 Jun 30;78(2):146-9. |
| PMID 9674905 |
| Expression of leukemia inhibitory factor (LIF)/interleukin-6 family cytokines and receptors during in vitro osteogenesis: differential regulation by dexamethasone and LIF. |
| Liu F, Aubin JE, Malaval L. |
| Bone. 2002 Jul;31(1):212-9. |
| PMID 12110437 |
| Mutations in the immunoglobulin-like domain of gp190, the leukemia inhibitory factor (LIF) receptor, increase or decrease its affinity for LIF. |
| Bitard J, Daburon S, Duplomb L, Blanchard F, Vuisio P, Jacques Y, Godard A, Heath JK, Moreau JF, Taupin JL. |
| J Biol Chem. 2003 May 2;278(18):16253-61. Epub 2003 Feb 24. |
| PMID 12601009 |
| The unsolved enigmas of leukemia inhibitory factor. |
| Metcalf D. |
| Stem Cells. 2003;21(1):5-14. |
| PMID 12529546 |
| Null leukemia inhibitory factor receptor (LIFR) mutations in Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome. |
| Dagoneau N, Scheffer D, Huber C, Al-Gazali LI, Di Rocco M, Godard A, Martinovic J, Raas-Rothschild A, Sigaudy S, Unger S, Nicole S, Fontaine B, Taupin JL, Moreau JF, Superti-Furga A, Le Merrer M, Bonaventure J, Munnich A, Legeai-Mallet L, Cormier-Daire V. |
| Am J Hum Genet. 2004 Feb;74(2):298-305. Epub 2004 Jan 21. |
| PMID 14740318 |
| Mutation analysis of leukemia inhibitory factor-receptor (LIF-R) in ACTH-secreting pituitary adenomas. |
| Heutling D, Dieterich KD, Buchfelder M, Lehnert H. |
| Exp Clin Endocrinol Diabetes. 2004 Sep;112(8):458-61. |
| PMID 15372367 |
| Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression. |
| Kamohara H, Ogawa M, Ishiko T, Sakamoto K, Baba H. |
| Int J Oncol. 2007 Apr;30(4):977-83. |
| PMID 17332938 |
| Transregulation of leukemia inhibitory (corrected) factor receptor expression and function by growth factors in neuroblastoma cells. |
| Port MD, Laszlo GS, Nathanson NM. |
| J Neurochem. 2008 Aug;106(4):1941-51. Epub 2008 Jul 4. |
| PMID 18624908 |
| Flow cytometry analysis of neural differentiation markers expression in human glioblastomas may predict their response to chemotherapy. |
| Balik V, Mirossay P, Bohus P, Sulla I, Mirossay L, Sarissky M. |
| Cell Mol Neurobiol. 2009 Sep;29(6-7):845-58. Epub 2009 Mar 14. |
| PMID 19288188 |
| Abnormal oral-pharyngeal swallowing as cause of morbidity and early death in Stuve-Wiedemann syndrome. |
| Corona-Rivera JR, Cormier-Daire V, Dagoneau N, Coello-Ramirez P, Lopez-Marure E, Romo-Huerta CO, Silva-Baez H, Aguirre-Salas LM, Estrada-Solorio MI. |
| Eur J Med Genet. 2009 Jul-Aug;52(4):242-6. Epub 2009 Apr 14. |
| PMID 19371797 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 12-2009 | Nathalie Dagoneau, Valérie Cormier-Daire |
| Department of Genetics and INSERM U781, Paris Descartes University, Tour Lavoisier, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France |
| Citation |
| This paper should be referenced as such : |
| Dagoneau N, Cormier-Daire V . LIFR (leukemia inhibitory factor receptor alpha). Atlas Genet Cytogenet Oncol Haematol. December 2009 . URL : http://AtlasGeneticsOncology.org/Genes/LIFRID410ch5p13.html |
This paper is referenced by INIST as such : |
| http://documents.irevues.inist.fr/bitstream/2042/44857/1/12-2009-LIFRID410ch5p13.pdf [ Bibliographic record ] |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Wed May 1 12:54:40 CEST 2013 |
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