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Gene Review

Lifr  -  leukemia inhibitory factor receptor alpha

Rattus norvegicus

Synonyms: LIF receptor, LIF-R, Leukemia inhibitory factor receptor
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Disease relevance of Lifr


High impact information on Lifr

  • We show here that neural precursor cells isolated from embryonic rat cortices abundantly secrete leukemia inhibitory factor (LIF) and express its receptor components, gp130 and LIF receptor [5].
  • In conclusion, these results indicate that transformed liver cells frequently undergo epigenetic alterations that suppress LIFR gene expression and modify the responsiveness to this IL-6 type cytokine [4].
  • Demethylation and remethylation of the CpG island within the LIFR promoter that is active in normal liver cells correlate with increased and decreased usage of this promoter in H-35 cells [4].
  • Analyses of the activation level of leukemia inhibitory factor receptor beta- and signal transducer and activator of transcription 3-signaling molecules in response to exogenous CNTF revealed an increased tyrosine phosphorylation positively correlated with the twitch tension developed by the soleus muscle of the animals [6].
  • On the contrary, overexpression of LIFR retards the growth of neurites [7].

Biological context of Lifr

  • Attenuation of LIFR signaling through stable transfection of antisense- or dominant negative-LIFR constructs enhances NGF-induced neurite extension in PC12 cells [7].
  • Taken together, our findings demonstrate that LIFR expression can be specifically induced by NGF and, besides its known function in cell survival and phenotype development, activated LIFR signaling can exert negative regulatory effects on neurite extension and branching of sympathetic neurons [7].
  • This truncated form, which is unable to bind LIF, was the only form expressed in meiotic germ cells, suggesting an original down-regulation process of LIF-R expression during spermatogenesis [8].
  • The rLIFR alpha protein shows a high degree of similarity to mouse and human LIF receptor alpha-chain protein (89% and 76% amino acid sequence identities, respectively) [9].
  • Thus, we studied the level of expression and cellular distribution of transcripts for LIF, its receptor (LIFR), and signal transducing subunit gp13O during rat liver regeneration after both simple partial hepatectomy (PH) and the oval cell activation induced by the combination of 2-acetylaminofluorene and PH [10].

Anatomical context of Lifr


Associations of Lifr with chemical compounds


Physical interactions of Lifr

  • CONCLUSIONS: Array analysis revealed changes in mRNA levels of several genes not previously associated with activation of the gp130/LIF receptor complex [13].

Other interactions of Lifr

  • Leukemia inhibitory factor receptor and gp130 were expressed in neurons, and the ischemic damage of these proteins was rescued in the high-LIF group [1].
  • Expression of CNTF/LIF-receptor components and activation of STAT3 signaling in axotomized facial motoneurons: evidence for a sequential postlesional function of the cytokines [14].
  • In TGR, the increased level of LIF was accompanied by a decrease in mRNA levels for LIFR and CNTFR [15].
  • A mild and late induction of the IL-6R, LIF-R, and IL-11R occurred after seizure with a scattered distribution [16].

Analytical, diagnostic and therapeutic context of Lifr

  • Real-time PCR analysis revealed that LIF mRNA expression was significantly increased from day 1 to day 7 after reperfusion and that LIFR mRNA was upregulated from day 4 to day 14 [3].
  • In addition to the 190-kDa LIF-R, Western blot analysis revealed the presence of a 50- to 60-kDa C-terminal gp190 isoform [8].
  • 6. The percentage of neurones surrounded by TH-IR baskets within the L3 and L4 dorsal root ganglia following sciatic axotomy was significantly reduced in animals treated continuously for 2 weeks with a monoclonal antibody against the LIF receptor motif, gp130 (0.833 mg ml-1) (P < 0.05, Mann-Whitney U test) [17].
  • In situ hybridization clearly revealed a strong expression of LIF, LIFR, and gp13O in the oval cells and demonstrated only a weak expression in the parenchyma [10].


  1. Activation of cytokine signaling through leukemia inhibitory factor receptor (LIFR)/gp130 attenuates ischemic brain injury in rats. Suzuki, S., Yamashita, T., Tanaka, K., Hattori, H., Sawamoto, K., Okano, H., Suzuki, N. J. Cereb. Blood Flow Metab. (2005) [Pubmed]
  2. Gene expression of receptors for IL-6, LIF, and CNTF in regenerating skeletal muscles. Kami, K., Morikawa, Y., Sekimoto, M., Senba, E. J. Histochem. Cytochem. (2000) [Pubmed]
  3. Leukemia inhibitory factor is involved in tubular regeneration after experimental acute renal failure. Yoshino, J., Monkawa, T., Tsuji, M., Hayashi, M., Saruta, T. J. Am. Soc. Nephrol. (2003) [Pubmed]
  4. DNA methylation controls the responsiveness of hepatoma cells to leukemia inhibitory factor. Blanchard, F., Tracy, E., Smith, J., Chattopadhyay, S., Wang, Y., Held, W.A., Baumann, H. Hepatology (2003) [Pubmed]
  5. Developmental stage-dependent self-regulation of embryonic cortical precursor cell survival and differentiation by leukemia inhibitory factor. Chang, M.Y., Park, C.H., Son, H., Lee, Y.S., Lee, S.H. Cell Death Differ. (2004) [Pubmed]
  6. Ciliary neurotrophic factor is a regulator of muscular strength in aging. Guillet, C., Auguste, P., Mayo, W., Kreher, P., Gascan, H. J. Neurosci. (1999) [Pubmed]
  7. Leukemia inhibitory factor receptor signaling negatively modulates nerve growth factor-induced neurite outgrowth in PC12 cells and sympathetic neurons. Ng, Y.P., He, W., Ip, N.Y. J. Biol. Chem. (2003) [Pubmed]
  8. Identification of the leukemia inhibitory factor cell targets within the rat testis. Dorval-Coiffec, I., Delcros, J.G., Hakovirta, H., Toppari, J., Jégou, B., Piquet-Pellorce, C. Biol. Reprod. (2005) [Pubmed]
  9. Molecular cloning of rat leukemia inhibitory factor receptor alpha-chain gene and its expression during pregnancy. Aikawa, J., Ikeda-Naiki, S., Ohgane, J., Min, K.S., Imamura, T., Sasai, K., Shiota, K., Ogawa, T. Biochim. Biophys. Acta (1997) [Pubmed]
  10. Expression of leukemia inhibitory factor and its receptor during liver regeneration in the adult rat. Omori, N., Evarts, R.P., Omori, M., Hu, Z., Marsden, E.R., Thorgeirsson, S.S. Lab. Invest. (1996) [Pubmed]
  11. Ciliary neurotrophic factor and its receptors are differentially expressed in the optic nerve transected adult rat retina. Sarup, V., Patil, K., Sharma, S.C. Brain Res. (2004) [Pubmed]
  12. Regulation of signal transducer, GP13O and the LIF receptor in acute inflammation in vivo. Geisterfer, M., Gauldie, J. Cytokine (1996) [Pubmed]
  13. Leukaemia inhibitory factor alters expression of genes involved in rat cardiomyocyte energy metabolism. Florholmen, G., Andersson, K.B., Yndestad, A., Austbø, B., Henriksen, U.L., Christensen, G. Acta Physiol. Scand. (2004) [Pubmed]
  14. Expression of CNTF/LIF-receptor components and activation of STAT3 signaling in axotomized facial motoneurons: evidence for a sequential postlesional function of the cytokines. Haas, C.A., Hofmann, H.D., Kirsch, M. J. Neurobiol. (1999) [Pubmed]
  15. Increased expression of IL-6 and LIF in the hypertrophied left ventricle of TGR(mRen2)27 and SHR rats. Kurdi, M., Randon, J., Cerutti, C., Bricca, G. Mol. Cell. Biochem. (2005) [Pubmed]
  16. Spatiotemporal distribution of gp130 cytokines and their receptors after status epilepticus: comparison with neuronal degeneration and microglial activation. Rosell, D.R., Nacher, J., Akama, K.T., McEwen, B.S. Neuroscience (2003) [Pubmed]
  17. Leukemia inhibitory factor induces sympathetic sprouting in intact dorsal root ganglia in the adult rat in vivo. Thompson, S.W., Majithia, A.A. J. Physiol. (Lond.) (1998) [Pubmed]
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