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Gene Review

Lifr  -  leukemia inhibitory factor receptor

Mus musculus

Synonyms: A230075M04Rik, AW061234, D-factor/LIF receptor, LIF, LIF receptor, ...
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Disease relevance of Lifr


High impact information on Lifr


Biological context of Lifr


Anatomical context of Lifr


Associations of Lifr with chemical compounds

  • 5. Despite a 3-fold induction of hypothalamic CRH mRNA, pituitary POMC mRNA and RU486-induced ACTH levels were decreased in Lifr -/- mice [10].
  • A strong level of LIFR mRNA signal was detected in the luminal epithelium on day 5 of pregnancy [6].
  • For example, a transient overlapping expression of LIFR and gp130 was evident at 12 h after estrogen-induced termination of delayed implantation [13].
  • We found that expression of c-Fos, c-Jun, and JunB was induced upon LIF treatment whereas that of JunD, the tyrosine phosphatase ESP, and the components of the LIF receptor remained unaffected [14].
  • Because corticosterone is known to have a broad range of effects and LIF function has been associated with the hypothalamo-pituitary-adrenal axis, this study was designed to determine the role for LIFR in the fetus when exposed to the elevated maternal glucocorticoid levels of late gestation [15].

Physical interactions of Lifr

  • Because the action of LIF is indirect and mediated by stromal cells, we hypothesized that LIF binds to the LIF receptor on AC6.21 stromal cells, leading to up-regulated production of stem cell expansion promoting factor (SCEPF) and/or down-regulated production of stem cell expansion inhibitory factor (SCEIF) [16].
  • The low-affinity receptor for leukemia inhibitory factor (LIFR) interacts with gp130 to induce an intracellular signal cascade [17].
  • LIF-R and IP-R activation induced binding of CREB and/or ATF-1 to C/EBP promoters and CREB-dependent transcription [18].

Regulatory relationships of Lifr


Other interactions of Lifr


Analytical, diagnostic and therapeutic context of Lifr


  1. Suppressor of cytokine signaling 3 limits protection of leukemia inhibitory factor receptor signaling against central demyelination. Emery, B., Cate, H.S., Marriott, M., Merson, T., Binder, M.D., Snell, C., Soo, P.Y., Murray, S., Croker, B., Zhang, J.G., Alexander, W.S., Cooper, H., Butzkueven, H., Kilpatrick, T.J. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  2. Cardiotrophin-1 activates a distinct form of cardiac muscle cell hypertrophy. Assembly of sarcomeric units in series VIA gp130/leukemia inhibitory factor receptor-dependent pathways. Wollert, K.C., Taga, T., Saito, M., Narazaki, M., Kishimoto, T., Glembotski, C.C., Vernallis, A.B., Heath, J.K., Pennica, D., Wood, W.I., Chien, K.R. J. Biol. Chem. (1996) [Pubmed]
  3. The leukemia inhibitory factor receptor gene is not involved in the etiology of pituitary dwarfism in German shepherd dogs. Hanson, J.M., Mol, J.A., Leegwater, P.A., Kooistra, H.S., Meij, B.P. Res. Vet. Sci. (2006) [Pubmed]
  4. LIF receptor signaling limits immune-mediated demyelination by enhancing oligodendrocyte survival. Butzkueven, H., Zhang, J.G., Soilu-Hanninen, M., Hochrein, H., Chionh, F., Shipham, K.A., Emery, B., Turnley, A.M., Petratos, S., Ernst, M., Bartlett, P.F., Kilpatrick, T.J. Nat. Med. (2002) [Pubmed]
  5. Essential function of LIF receptor in motor neurons. Li, M., Sendtner, M., Smith, A. Nature (1995) [Pubmed]
  6. Expression of leukemia inhibitory factor receptor and gp130 in mouse uterus during early pregnancy. Ni, H., Ding, N.Z., Harper, M.J., Yang, Z.M. Mol. Reprod. Dev. (2002) [Pubmed]
  7. The ciliary neurotrophic factor/leukemia inhibitory factor/gp130 receptor complex operates in the maintenance of mammalian forebrain neural stem cells. Shimazaki, T., Shingo, T., Weiss, S. J. Neurosci. (2001) [Pubmed]
  8. Leukemia inhibitory factor and its receptor promote adipocyte differentiation via the mitogen-activated protein kinase cascade. Aubert, J., Dessolin, S., Belmonte, N., Li, M., McKenzie, F.R., Staccini, L., Villageois, P., Barhanin, B., Vernallis, A., Smith, A.G., Ailhaud, G., Dani, C. J. Biol. Chem. (1999) [Pubmed]
  9. Leukemia inhibitory factor, leukemia inhibitory factor receptor, and glycoprotein 130 in rhesus monkey uterus during menstrual cycle and early pregnancy. Yue, Z.P., Yang, Z.M., Wei, P., Li, S.J., Wang, H.B., Tan, J.H., Harper, M.J. Biol. Reprod. (2000) [Pubmed]
  10. Leukemia inhibitory factor signaling is implicated in embrionic development of the HPA axis. Ware, C.B., Kariagina, A., Zonis, S., Alon, D., Chesnokova, V. FEBS Lett. (2005) [Pubmed]
  11. SOCS3: an essential regulator of LIF receptor signaling in trophoblast giant cell differentiation. Takahashi, Y., Carpino, N., Cross, J.C., Torres, M., Parganas, E., Ihle, J.N. EMBO J. (2003) [Pubmed]
  12. Cytoplasmic domains of the leukemia inhibitory factor receptor required for STAT3 activation, differentiation, and growth arrest of myeloid leukemic cells. Tomida, M., Heike, T., Yokota, T. Blood (1999) [Pubmed]
  13. Evidence for heterodimeric association of leukemia inhibitory factor (LIF) receptor and gp130 in the mouse uterus for LIF signaling during blastocyst implantation. Song, H., Lim, H. Reproduction (2006) [Pubmed]
  14. Role of suppressors of cytokine signaling (Socs) in leukemia inhibitory factor (LIF) -dependent embryonic stem cell survival. Duval, D., Reinhardt, B., Kedinger, C., Boeuf, H. FASEB J. (2000) [Pubmed]
  15. Late gestation modulation of fetal glucocorticoid effects requires the receptor for leukemia inhibitory factor: an observational study. Ware, C.B., Nelson, A.M., Liggitt, D. Reprod. Biol. Endocrinol. (2003) [Pubmed]
  16. A secreted and LIF-mediated stromal cell-derived activity that promotes ex vivo expansion of human hematopoietic stem cells. Shih, C.C., Hu, M.C., Hu, J., Weng, Y., Yazaki, P.J., Medeiros, J., Forman, S.J. Blood (2000) [Pubmed]
  17. Targeted disruption of the low-affinity leukemia inhibitory factor receptor gene causes placental, skeletal, neural and metabolic defects and results in perinatal death. Ware, C.B., Horowitz, M.C., Renshaw, B.R., Hunt, J.S., Liggitt, D., Koblar, S.A., Gliniak, B.C., McKenna, H.J., Papayannopoulou, T., Thoma, B. Development (1995) [Pubmed]
  18. Activation of extracellular signal-regulated kinases and CREB/ATF-1 mediate the expression of CCAAT/enhancer binding proteins beta and -delta in preadipocytes. Belmonte, N., Phillips, B.W., Massiera, F., Villageois, P., Wdziekonski, B., Saint-Marc, P., Nichols, J., Aubert, J., Saeki, K., Yuo, A., Narumiya, S., Ailhaud, G., Dani, C. Mol. Endocrinol. (2001) [Pubmed]
  19. Ciliary neurotrophic factor may activate mature astrocytes via binding with the leukemia inhibitory factor receptor. Monville, C., Coulpier, M., Conti, L., De-Fraja, C., Dreyfus, P., Fages, C., Riche, D., Tardy, M., Cattaneo, E., Peschanski, M. Mol. Cell. Neurosci. (2001) [Pubmed]
  20. Loss of leukemia inhibitory factor receptor beta or cardiotrophin-1 causes similar deficits in preganglionic sympathetic neurons and adrenal medulla. Oberle, S., Schober, A., Meyer, V., Holtmann, B., Henderson, C., Sendtner, M., Unsicker, K. J. Neurosci. (2006) [Pubmed]
  21. LIF receptor signaling modulates neural stem cell renewal. Pitman, M., Emery, B., Binder, M., Wang, S., Butzkueven, H., Kilpatrick, T.J. Mol. Cell. Neurosci. (2004) [Pubmed]
  22. mRNA expression of leukaemia inhibitory factor (LIF) and its receptor subunits glycoprotein 130 and LIF-receptor-beta in bovine embryos derived in vitro or in vivo. Eckert, J., Niemann, H. Mol. Hum. Reprod. (1998) [Pubmed]
  23. The signaling pathway of cardiotrophin-1 is not activated in hypertrophied ventricles of carnitine-deficient juvenile visceral steatosis (JVS) mice. Yoshida, G., Horiuchi, M., Kobayashi, K., Jalil, M.D., Iijima, M., Hagihara, S., Nagao, N., Saheki, T. In Vivo (2000) [Pubmed]
  24. Expression of interleukin-6 receptor, leukemia inhibitory factor receptor and glycoprotein 130 in the murine cerebellum and neuropathological effect of leukemia inhibitory factor on cerebellar Purkinje cells. Morikawa, Y., Tohya, K., Tamura, S., Ichihara, M., Miyajima, A., Senba, E. Neuroscience (2000) [Pubmed]
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