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Gene Review

Il6st  -  interleukin 6 signal transducer

Mus musculus

Synonyms: 5133400A03Rik, AA389424, BB405851, CD130, D13Ertd699e, ...
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Disease relevance of Il6st


High impact information on Il6st

  • The latent transcription factor Stat3 is activated by gp130, the common receptor for the interleukin (IL)-6 cytokine family and other growth factor and cytokine receptors [5].
  • Ligand-induced dimerization of gp130 leads to activation of the Stat1, Stat3 and Shp2-Ras-Erk signaling pathways [5].
  • Hyperactivation of Stat3 in gp130 mutant mice promotes gastric hyperproliferation and desensitizes TGF-beta signaling [5].
  • In contrast, mice harboring the reciprocal mutation ablating STAT1/3 signaling (gp130(Delta STAT)), or deficient in IL-6-mediated gp130 signaling (IL-6(-/-) mice), showed impaired colonic mucosal wound healing [6].
  • Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice [6].

Chemical compound and disease context of Il6st


Biological context of Il6st


Anatomical context of Il6st

  • RESULTS: Cre expression started at day 10.5 postconception, and a complete deletion of gp130 in hepatocytes was found at day 14 during liver development [1].
  • CNTF/LIF/gp130 receptor complex signaling maintains a VZ precursor differentiation gradient in the developing ventral forebrain [12].
  • These results demonstrate a novel region-specific role for CNTF/LIF/gp130 signaling in the development of the germinal layers of the embryonic telencephalon [12].
  • In addition, the agonistic gp130 mAb may be used as growth factors for maintenance and expansion of stem cells prior to grafting [13].
  • Since hematopoietic stem cells express gp130 on their plasma membrane, it was anticipated that the agonistic anti-gp130 mAb could stimulate the proliferation of these stem cells [13].

Associations of Il6st with chemical compounds

  • For example, a transient overlapping expression of LIFR and gp130 was evident at 12 h after estrogen-induced termination of delayed implantation [14].
  • We show here that JAK2 kinase is rapidly tyrosine phosphorylated in mouse embryonic stem cells whose pluripotentiality is maintained only by gp130-sharing cytokines after stimulation that is known to induce gp130 homodimerization [15].
  • The presence of LIF receptor and gp130 in the luminal epithelium on day 4 and in the stroma on day 5 may indicate the site of the high affinity LIF receptor [16].
  • The interleukin (IL)-6 family cytokines utilize membrane glycoprotein gp130 in common as a critical signal-transducing receptor component [17].
  • Roles of lipid rafts in integrin-dependent adhesion and gp130 signalling pathway in mouse embryonic neural precursor cells [18].

Physical interactions of Il6st


Enzymatic interactions of Il6st


Regulatory relationships of Il6st


Other interactions of Il6st

  • To define the IL-6-dependent intracellular pathways more specifically, we generated a hepatocyte-specific gp130 knockout mouse [1].
  • Taken together, our results suggest that the gp130-mediated activation of JAK2/STAT3 signaling pathway may play a key role in the induction of astrogliosis [10].
  • Ciliary neurotrophic factor, but not oncostatin M, had the same effect, although they both bind to the IL-6ST (gp130) receptor [26].
  • Similar expression patterns for LIFR and gp130 were observed when a delayed implantation model was used [14].
  • Glycoprotein130 (gp130) and Notch signaling are thought to participate in neural stem cell (NSC) self-renewal [24].

Analytical, diagnostic and therapeutic context of Il6st

  • Thus our results suggest that the role of gp130-dependent signaling is not a direct influence on cell cycle progression after partial hepatectomy but is to activate protective pathways important to enable hepatocyte proliferation [11].
  • By RT-PCR analysis, gp130 mRNA was detected in all of the uteri from day 1-8 of pregnancy, being at the highest level on day 4 of pregnancy [27].
  • The aim of this study was to assess the expression and regulation of LIF receptor (LIFR) and gp130 mRNA in mouse uterus during early pregnancy using in situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR) [27].
  • Consistent with these findings, ovariectomy in mice caused an increase in expression of gp80, gp130, and IL-6 mRNAs in ex vivo bone marrow cell cultures as determined by quantitative reverse transcription (RT)-PCR, and confirmed on an individual cell basis using in situ RT-PCR [28].
  • Although gp130 activation is observed transiently during transverse aortic constriction (TAC), its mechanism of inactivation is largely unknown in cardiomyocytes [29].


  1. Lack of gp130 expression in hepatocytes promotes liver injury. Streetz, K.L., Wüstefeld, T., Klein, C., Kallen, K.J., Tronche, F., Betz, U.A., Schütz, G., Manns, M.P., Müller, W., Trautwein, C. Gastroenterology (2003) [Pubmed]
  2. Continuous activation of gp130, a signal-transducing receptor component for interleukin 6-related cytokines, causes myocardial hypertrophy in mice. Hirota, H., Yoshida, K., Kishimoto, T., Taga, T. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  3. Defective gp130-mediated signal transducer and activator of transcription (STAT) signaling results in degenerative joint disease, gastrointestinal ulceration, and failure of uterine implantation. Ernst, M., Inglese, M., Waring, P., Campbell, I.K., Bao, S., Clay, F.J., Alexander, W.S., Wicks, I.P., Tarlinton, D.M., Novak, U., Heath, J.K., Dunn, A.R. J. Exp. Med. (2001) [Pubmed]
  4. Contribution of interleukin-6/gp 130 signaling in hepatocytes to the inflammatory response in mice infected with Streptococcus pyogenes. Klein, C., Medina, E., Sander, L., Dierssen, U., Roskams, T., Mueller, W., Trautwein, C., Goldmann, O. J. Infect. Dis. (2007) [Pubmed]
  5. Hyperactivation of Stat3 in gp130 mutant mice promotes gastric hyperproliferation and desensitizes TGF-beta signaling. Jenkins, B.J., Grail, D., Nheu, T., Najdovska, M., Wang, B., Waring, P., Inglese, M., McLoughlin, R.M., Jones, S.A., Topley, N., Baumann, H., Judd, L.M., Giraud, A.S., Boussioutas, A., Zhu, H.J., Ernst, M. Nat. Med. (2005) [Pubmed]
  6. Reciprocal regulation of gastrointestinal homeostasis by SHP2 and STAT-mediated trefoil gene activation in gp130 mutant mice. Tebbutt, N.C., Giraud, A.S., Inglese, M., Jenkins, B., Waring, P., Clay, F.J., Malki, S., Alderman, B.M., Grail, D., Hollande, F., Heath, J.K., Ernst, M. Nat. Med. (2002) [Pubmed]
  7. The point mutation of tyrosine 759 of the IL-6 family cytokine receptor gp130 synergizes with HTLV-1 pX in promoting rheumatoid arthritis-like arthritis. Ishihara, K., Sawa, S., Ikushima, H., Hirota, S., Atsumi, T., Kamimura, D., Park, S.J., Murakami, M., Kitamura, Y., Iwakura, Y., Hirano, T. Int. Immunol. (2004) [Pubmed]
  8. Surface antigens of melanomas and melanocytes defined by mouse monoclonal antibodies: specificity analysis and comparison of antigen expression in cultured cells and tissues. Real, F.X., Houghton, A.N., Albino, A.P., Cordon-Cardo, C., Melamed, M.R., Oettgen, H.F., Old, L.J. Cancer Res. (1985) [Pubmed]
  9. An epitope on the surface envelope glycoprotein (gp130) of simian immunodeficiency virus (SIVmac) involved in viral neutralization and T cell activation. Torres, J.V., Malley, A., Banapour, B., Anderson, D.E., Axthelm, M.K., Gardner, M.B., Benjamini, E. AIDS Res. Hum. Retroviruses (1993) [Pubmed]
  10. Induction of gp130-related cytokines and activation of JAK2/STAT3 pathway in astrocytes precedes up-regulation of glial fibrillary acidic protein in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of neurodegeneration: key signaling pathway for astrogliosis in vivo? Sriram, K., Benkovic, S.A., Hebert, M.A., Miller, D.B., O'Callaghan, J.P. J. Biol. Chem. (2004) [Pubmed]
  11. Interleukin-6/glycoprotein 130-dependent pathways are protective during liver regeneration. Wuestefeld, T., Klein, C., Streetz, K.L., Betz, U., Lauber, J., Buer, J., Manns, M.P., Müller, W., Trautwein, C. J. Biol. Chem. (2003) [Pubmed]
  12. CNTF/LIF/gp130 receptor complex signaling maintains a VZ precursor differentiation gradient in the developing ventral forebrain. Gregg, C., Weiss, S. Development (2005) [Pubmed]
  13. Interleukin-6 signal transducer gp130 has specific binding sites for different cytokines as determined by antagonistic and agonistic anti-gp130 monoclonal antibodies. Wijdenes, J., Heinrich, P.C., Müller-Newen, G., Roche, C., Gu, Z.J., Clément, C., Klein, B. Eur. J. Immunol. (1995) [Pubmed]
  14. 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]
  15. Activation of JAK2 kinase mediated by the interleukin 6 signal transducer gp130. Narazaki, M., Witthuhn, B.A., Yoshida, K., Silvennoinen, O., Yasukawa, K., Ihle, J.N., Kishimoto, T., Taga, T. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  16. Leukemia inhibitory factor, LIF receptor, and gp130 in the mouse uterus during early pregnancy. Yang, Z.M., Le, S.P., Chen, D.B., Cota, J., Siero, V., Yasukawa, K., Harper, M.J. Mol. Reprod. Dev. (1995) [Pubmed]
  17. Astrocyte differentiation of fetal neuroepithelial cells by interleukin-11 via activation of a common cytokine signal transducer, gp130, and a transcription factor, STAT3. Yanagisawa, M., Nakashima, K., Arakawa, H., Ikenaka, K., Yoshida, K., Kishimoto, T., Hisatsune, T., Taga, T. J. Neurochem. (2000) [Pubmed]
  18. Roles of lipid rafts in integrin-dependent adhesion and gp130 signalling pathway in mouse embryonic neural precursor cells. Yanagisawa, M., Nakamura, K., Taga, T. Genes Cells (2004) [Pubmed]
  19. Inverse regulation of interleukin-6 (IL-6) and IL-6 receptor in histamine deficient histidine decarboxylase-knock-out mice. Horváth, B.V., Falus, A., Tóth, S., Szalai, C., Lázár-Molnár, E., Holub, M.C., Buzás, E., Nagy, A., Fulop, A.K. Immunol. Lett. (2002) [Pubmed]
  20. 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]
  21. Identification of ligand-binding site III on the immunoglobulin-like domain of the granulocyte colony-stimulating factor receptor. Layton, J.E., Hall, N.E., Connell, F., Venhorst, J., Treutlein, H.R. J. Biol. Chem. (2001) [Pubmed]
  22. Calmodulin-dependent protein kinases phosphorylate gp130 at the serine-based dileucine internalization motif. Gibson, R.M., Laszlo, G.S., Nathanson, N.M. Biochim. Biophys. Acta (2005) [Pubmed]
  23. SOCS3 regulates the plasticity of gp130 signaling. Lang, R., Pauleau, A.L., Parganas, E., Takahashi, Y., Mages, J., Ihle, J.N., Rutschman, R., Murray, P.J. Nat. Immunol. (2003) [Pubmed]
  24. Glycoprotein 130 signaling regulates Notch1 expression and activation in the self-renewal of mammalian forebrain neural stem cells. Chojnacki, A., Shimazaki, T., Gregg, C., Weinmaster, G., Weiss, S. J. Neurosci. (2003) [Pubmed]
  25. Astrocyte differentiation of fetal neuroepithelial cells involving cardiotrophin-1-induced activation of STAT3. Ochiai, W., Yanagisawa, M., Takizawa, T., Nakashima, K., Taga, T. Cytokine (2001) [Pubmed]
  26. Leukemia inhibitory factor enhances formation of germ cell colonies in neonatal mouse testis culture. Kanatsu-Shinohara, M., Inoue, K., Ogonuki, N., Miki, H., Yoshida, S., Toyokuni, S., Lee, J., Ogura, A., Shinohara, T. Biol. Reprod. (2007) [Pubmed]
  27. 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]
  28. Regulation of the gp80 and gp130 subunits of the IL-6 receptor by sex steroids in the murine bone marrow. Lin, S.C., Yamate, T., Taguchi, Y., Borba, V.Z., Girasole, G., O'Brien, C.A., Bellido, T., Abe, E., Manolagas, S.C. J. Clin. Invest. (1997) [Pubmed]
  29. Suppressor of cytokine signaling-3 is a biomechanical stress-inducible gene that suppresses gp130-mediated cardiac myocyte hypertrophy and survival pathways. Yasukawa, H., Hoshijima, M., Gu, Y., Nakamura, T., Pradervand, S., Hanada, T., Hanakawa, Y., Yoshimura, A., Ross, J., Chien, K.R. J. Clin. Invest. (2001) [Pubmed]
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