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Glycoprotein 130

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Title: Glycoprotein 130  
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Subject: Interleukin-6 receptor, CXCR6, IL3RA, CCR9, C-C chemokine receptor type 7
Collection: Glycoproteins, Molecular Biology, Type I Cytokine Receptors
Publisher: World Heritage Encyclopedia

Glycoprotein 130

Interleukin 6 signal transducer

Gp130 extracellular domain crystal structure from PDB 1p9m.
Available structures
PDB Ortholog search: PDBe, RCSB
Symbols  ; CD130; CDW130; GP130; IL-6RB
External IDs GeneCards:
Species Human Mouse
RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)
PubMed search

Glycoprotein 130 (also known as gp130, IL6ST, IL6-beta or CD130) is a transmembrane protein which is the founding member of the class of all cytokine receptors. It forms one subunit of the type I cytokine receptor within the IL-6 receptor family. It is often referred to as the common gp130 subunit, and is important for signal transduction following cytokine engagement. As with other type I cytokine receptors, gp130 possesses a WSXWS amino acid motif that ensures correct protein folding and ligand binding. It interacts with Janus kinases to elicit an intracellular signal following receptor interaction with its ligand. Structurally, gp130 is composed of five fibronectin type-III domains and one immunoglobulin-like C2-type (immunoglobulin-like) domain in its extracellular portion.[1][2]


  • Characteristics 1
  • Loss of gp130 2
  • Signal transduction 3
  • Interactions 4
  • References 5
  • Further reading 6
  • External links 7


The members of the IL-6 receptor family all complex with gp130 for signal transduction. For example, IL-6 binds to the IL-6 Receptor. The complex of these two proteins then associates with gp130. This complex of 3 proteins then homodimerizes to form a hexameric complex which can produce downstream signals.[3] There are many other proteins which associate with gp130, such as cardiotrophin 1 (CT-1), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM), and IL-11.[4] There are also several other proteins which have structural similarity to gp130 and contain the WSXWS motif and preserved cysteine residues. Members of this group include LIF-R, OSM-R, and G-CSF-R.

Loss of gp130

gp130 is an important part of many different types of signaling complexes. Inactivation of gp130 is lethal to mice.[5] Homozygous mice who are born show a number of defects including impaired development of the ventricular myocardium. Haematopoietic effects included reduced numbers of stem cells in the spleen and liver.

Signal transduction

gp130 has no intrinsic tyrosine kinase activity. Instead, it is phosphorylated on tyrosine residues after complexing with other proteins. The phosphorylation leads to association with JAK/Tyk tyrosine kinases and STAT protein transcription factors.[6] In particular, STAT-3 is activated which leads to the activation of many downstream genes. Other pathways activated include RAS and MAPK signaling.


Glycoprotein 130 has been shown to interact with TLE1,[7] SOCS3,[8] HER2/neu,[9] PTPN11,[8][10][11] Leukemia inhibitory factor receptor,[12][13] Grb2,[14] Janus kinase 1[11][15][16] and SHC1.[17]


  1. ^ Hibi et al.; Murakami, M; Saito, M; Hirano, T; Taga, T; Kishimoto, T (1990). "Molecular cloning and expression of an IL-6 signal transducer, gp130". Cell 63 (6): 1149–1157.  
  2. ^ Bravo et al.; Staunton, D; Heath, JK; Jones, EY (1998). "Crystal structure of a cytokine-binding region of gp130". EMBO J 17 (6): 1665–1674.  
  3. ^ Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, Taga T, Kishimoto T (1993). "IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase". Science 260 (5115): 1808–1810.  
  4. ^ Kishimoto T, Akira S, Narazaki M, Taga T (1995). "Interleukin-6 family of cytokines and gp130". Blood 86 (4): 1243–1254.  
  5. ^ Yoshida K, Taga T, Saito M, Suematsu S, Kumanogoh A, Tanaka T, Fujiwara H, Hirata M, Yamagami T, Nakahata T, Hirabayashi T, Yoneda Y, Tanaka K, Wang W-Z, Mori C, Shiota K, Yoshida N, Kishimoto T (1996). "Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders". Proc. Natl. Acad. Sci. USA 93 (1): 407–411.  
  6. ^ Kishimoto T, Taga T, Akira S (1994). "Cytokine signal transduction". Cell 76 (2): 253–262.  
  7. ^ Liu, Fei; Liu Yin; Li Demin; Zhu Yong; Ouyang Weiming; Xie Xin; Jin Boquan (March 2002). "The transcription co-repressor TLE1 interacted with the intracellular region of gpl30 through its Q domain". Mol. Cell. Biochem. (Netherlands) 232 (1–2): 163–7.  
  8. ^ a b Lehmann, Ute; Schmitz Jochen, Weissenbach Manuela, Sobota Radoslaw M, Hortner Michael, Friederichs Kerstin, Behrmann Iris, Tsiaris William, Sasaki Atsuo, Schneider-Mergener Jens, Yoshimura Akihiko, Neel Benjamin G, Heinrich Peter C, Schaper Fred (January 2003). "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130". J. Biol. Chem. (United States) 278 (1): 661–71.  
  9. ^ Grant, Susan L; Hammacher Annet; Douglas Andrea M; Goss Geraldine A; Mansfield Rachel K; Heath John K; Begley C Glenn (January 2002). "An unexpected biochemical and functional interaction between gp130 and the EGF receptor family in breast cancer cells". Oncogene (England) 21 (3): 460–74.  
  10. ^ Anhuf, D; Weissenbach M; Schmitz J; Sobota R; Hermanns H M; Radtke S; Linnemann S; Behrmann I; Heinrich P C; Schaper F (September 2000). "Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation". J. Immunol. (UNITED STATES) 165 (5): 2535–43.  
  11. ^ a b Kim, H; Baumann H (December 1997). "Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells". J. Biol. Chem. (UNITED STATES) 272 (49): 30741–7.  
  12. ^ Timmermann, Andreas; Küster Andrea, Kurth Ingo, Heinrich Peter C, Müller-Newen Gerhard (June 2002). "A functional role of the membrane-proximal extracellular domains of the signal transducer gp130 in heterodimerization with the leukemia inhibitory factor receptor". Eur. J. Biochem. (Germany) 269 (11): 2716–26.  
  13. ^ Mosley, B; De Imus C; Friend D; Boiani N; Thoma B; Park L S; Cosman D (December 1996). "Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation". J. Biol. Chem. (UNITED STATES) 271 (51): 32635–43.  
  14. ^ Lee, I S; Liu Y; Narazaki M; Hibi M; Kishimoto T; Taga T (January 1997). "Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6". FEBS Lett. (NETHERLANDS) 401 (2–3): 133–7.  
  15. ^ Haan, C; Is'harc H, Hermanns H M, Schmitz-Van De Leur H, Kerr I M, Heinrich P C, Grötzinger J, Behrmann I (October 2001). "Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction". J. Biol. Chem. (United States) 276 (40): 37451–8.  
  16. ^ Haan, Claude; Heinrich Peter C; Behrmann Iris (January 2002). "Structural requirements of the interleukin-6 signal transducer gp130 for its interaction with Janus kinase 1: the receptor is crucial for kinase activation". Biochem. J. (England) 361 (Pt 1): 105–11.  
  17. ^ Giordano, V; De Falco G; Chiari R; Quinto I; Pelicci P G; Bartholomew L; Delmastro P; Gadina M; Scala G (May 1997). "Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase". J. Immunol. (UNITED STATES) 158 (9): 4097–103.  

Further reading

  • Ip NY, Nye SH, Boulton TG, et al. (1992). "CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130". Cell 69 (7): 1121–32.  
  • Hibi M, Murakami M, Saito M, et al. (1991). "Molecular cloning and expression of an IL-6 signal transducer, gp130". Cell 63 (6): 1149–57.  
  • Taga T, Hibi M, Hirata Y, et al. (1989). "Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130". Cell 58 (3): 573–81.  
  • Rodriguez C, Grosgeorge J, Nguyen VC, et al. (1995). "Human gp130 transducer chain gene (IL6ST) is localized to chromosome band 5q11 and possesses a pseudogene on chromosome band 17p11". Cytogenet. Cell Genet. 70 (1–2): 64–7.  
  • Narazaki M, Yasukawa K, Saito T, et al. (1993). "Soluble forms of the interleukin-6 signal-transducing receptor component gp130 in human serum possessing a potential to inhibit signals through membrane-anchored gp130". Blood 82 (4): 1120–6.  
  • Davis S, Aldrich TH, Stahl N, et al. (1993). "LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor". Science 260 (5115): 1805–8.  
  • Murakami M, Hibi M, Nakagawa N, et al. (1993). "IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase". Science 260 (5115): 1808–10.  
  • Sharkey AM, Dellow K, Blayney M, et al. (1996). "Stage-specific expression of cytokine and receptor messenger ribonucleic acids in human preimplantation embryos". Biol. Reprod. 53 (4): 974–81.  
  • Mosley B, De Imus C, Friend D, et al. (1997). "Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation". J. Biol. Chem. 271 (51): 32635–43.  
  • Lee IS, Liu Y, Narazaki M, et al. (1997). "Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6". FEBS Lett. 401 (2–3): 133–7.  
  • Auguste P, Guillet C, Fourcin M, et al. (1997). "Signaling of type II oncostatin M receptor". J. Biol. Chem. 272 (25): 15760–4.  
  • Schiemann WP, Bartoe JL, Nathanson NM (1997). "Box 3-independent signaling mechanisms are involved in leukemia inhibitory factor receptor alpha- and gp130-mediated stimulation of mitogen-activated protein kinase. Evidence for participation of multiple signaling pathways which converge at Ras". J. Biol. Chem. 272 (26): 16631–6.  
  • Diamant M, Rieneck K, Mechti N, et al. (1997). "Cloning and expression of an alternatively spliced mRNA encoding a soluble form of the human interleukin-6 signal transducer gp130". FEBS Lett. 412 (2): 379–84.  
  • Koshelnick Y, Ehart M, Hufnagl P, et al. (1997). "Urokinase receptor is associated with the components of the JAK1/STAT1 signaling pathway and leads to activation of this pathway upon receptor clustering in the human kidney epithelial tumor cell line TCL-598". J. Biol. Chem. 272 (45): 28563–7.  
  • Kim H, Baumann H (1998). "Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells". J. Biol. Chem. 272 (49): 30741–7.  
  • Bravo J, Staunton D, Heath JK, Jones EY (1998). "Crystal structure of a cytokine-binding region of gp130". EMBO J. 17 (6): 1665–74.  
  • Barton VA, Hudson KR, Heath JK (1999). "Identification of three distinct receptor binding sites of murine interleukin-11". J. Biol. Chem. 274 (9): 5755–61.  
  • Hirota H, Chen J, Betz UA, et al. (1999). "Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress". Cell 97 (2): 189–98.  
  • Tacken I, Dahmen H, Boisteau O, et al. (1999). "Definition of receptor binding sites on human interleukin-11 by molecular modeling-guided mutagenesis". Eur. J. Biochem. 265 (2): 645–55.  
  • Chung TD, Yu JJ, Kong TA, et al. (2000). "Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines". Prostate 42 (1): 1–7.  

External links

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