LIFR (leukemia inhibitory factor receptor alpha)

2009-12-01   Nathalie Dagoneau , Valérie Cormier-Daire 

Department of Genetics, INSERM U781, Paris Descartes University, Tour Lavoisier, Hopital Necker Enfants Malades, 149 rue de Sevres, 75015 Paris, France

Identity

HGNC
LOCATION
5p13.1
LOCUSID
ALIAS
CD118,LIF-R,SJS2,STWS,SWS
FUSION GENES

DNA/RNA

Atlas Image
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.

Proteins

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).
Atlas Image

Implicated in

Entity name
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 name
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 name
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 name
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 name
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.

Bibliography

Pubmed IDLast YearTitleAuthors
192881882009Flow cytometry analysis of neural differentiation markers expression in human glioblastomas may predict their response to chemotherapy.Balik V et al
126010092003Mutations in the immunoglobulin-like domain of gp190, the leukemia inhibitory factor (LIF) receptor, increase or decrease its affinity for LIF.Bitard J et al
96749051998Clinical homogeneity of the Stüve-Wiedemann syndrome and overlap with the Schwartz-Jampel syndrome type 2.Cormier-Daire V et al
193717972009Abnormal oral-pharyngeal swallowing as cause of morbidity and early death in Stüve-Wiedemann syndrome.Corona-Rivera JR et al
147403182004Null leukemia inhibitory factor receptor (LIFR) mutations in Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome.Dagoneau N et al
82764031993The 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 et al
153723672004Mutation analysis of leukemia inhibitory factor-receptor (LIF-R) in ACTH-secreting pituitary adenomas.Heutling D et al
173329382007Leukemia inhibitory factor functions as a growth factor in pancreas carcinoma cells: Involvement of regulation of LIF and its receptor expression.Kamohara H et al
75010191995Essential function of LIF receptor in motor neurons.Li M et al
121104372002Expression of leukemia inhibitory factor (LIF)/interleukin-6 family cytokines and receptors during in vitro osteogenesis: differential regulation by dexamethasone and LIF.Liu F et al
125295462003The unsolved enigmas of leukemia inhibitory factor.Metcalf D et al
186249082008Transregulation of leukemia inhibitory [corrected] factor receptor expression and function by growth factors in neuroblastoma cells.Port MD et al
92426671997Distinct roles for leukemia inhibitory factor receptor alpha-chain and gp130 in cell type-specific signal transduction.Starr R et al
51576491971[Congenital bowing of long bones--occurrence in two sisters].Stüve A et al
88648651996Structure of the gene encoding the human differentiation-stimulating factor/leukemia inhibitory factor receptor.Tomida M et al
77892611995Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death.Ware CB et al

Other Information

Locus ID:

NCBI: 3977
MIM: 151443
HGNC: 6597
Ensembl: ENSG00000113594

Variants:

dbSNP: 3977
ClinVar: 3977
TCGA: ENSG00000113594
COSMIC: LIFR

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000113594ENST00000263409P42702
ENSG00000113594ENST00000453190P42702
ENSG00000113594ENST00000506003H0YAF2
ENSG00000113594ENST00000506990D6RF33
ENSG00000113594ENST00000511561D6RJ94

Expression (GTEx)

0
10
20
30
40
50
60
70
80

Pathways

PathwaySourceExternal ID
Cytokine-cytokine receptor interactionKEGGko04060
Jak-STAT signaling pathwayKEGGko04630
Cytokine-cytokine receptor interactionKEGGhsa04060
Jak-STAT signaling pathwayKEGGhsa04630
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Immune SystemREACTOMER-HSA-168256
Cytokine Signaling in Immune systemREACTOMER-HSA-1280215
Signaling by InterleukinsREACTOMER-HSA-449147
Interleukin-6 family signalingREACTOMER-HSA-6783589
IL-6-type cytokine receptor ligand interactionsREACTOMER-HSA-6788467

References

Pubmed IDYearTitleCitations
230011832012LIFR is a breast cancer metastasis suppressor upstream of the Hippo-YAP pathway and a prognostic marker.147
219664842011Leukemia inhibitory factor enhances endometrial stromal cell decidualization in humans and mice.38
147403182004Null leukemia inhibitory factor receptor (LIFR) mutations in Stuve-Wiedemann/Schwartz-Jampel type 2 syndrome.36
187753322008Structural organization of a full-length gp130/LIF-R cytokine receptor transmembrane complex.32
233825632013Microglia and a functional type I IFN pathway are required to counter HSV-1-driven brain lateral ventricle enlargement and encephalitis.31
202374962010New genetic associations detected in a host response study to hepatitis B vaccine.27
225350172012Whole genome in vivo RNAi screening identifies the leukemia inhibitory factor receptor as a novel breast tumor suppressor.23
194532612009High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men.20
262493602015LIFR functions as a metastasis suppressor in hepatocellular carcinoma by negatively regulating phosphoinositide 3-kinase/AKT pathway.20
197330042010Leukemia inhibitory factor receptor (LIFR) is detected as a novel suppressor gene of hepatocellular carcinoma using double-combination array.19

Citation

Nathalie Dagoneau ; Valérie Cormier-Daire

LIFR (leukemia inhibitory factor receptor alpha)

Atlas Genet Cytogenet Oncol Haematol. 2009-12-01

Online version: http://atlasgeneticsoncology.org/gene/410/lifr