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glycoprotein 130

{{Short description|Mammalian protein found in Homo sapiens}}

{{about|the glycoprotein|the stimulant drug|G-130}}

{{Redirect|Cd130|the isotope of cadmium (Cd-130 or 130Cd)|Cadmium-130}}

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{{Infobox gene}}

Glycoprotein 130 (also known as gp130, IL6ST, IL6R-beta or CD130) is a transmembrane protein which is the founding member of the class of tall 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.{{cite journal | vauthors = Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T | title = Molecular cloning and expression of an IL-6 signal transducer, gp130 | journal = Cell | volume = 63 | issue = 6 | pages = 1149–1157 | year = 1990 | pmid = 2261637 | doi = 10.1016/0092-8674(90)90411-7 | s2cid = 30852638 }}{{cite journal | vauthors = Bravo J, Staunton D, Heath JK, Jones EY | title = Crystal structure of a cytokine-binding region of gp130 | journal = EMBO J | volume = 17 | issue = 6 | pages = 1665–1674 | year = 1998 | pmid = 9501088 | pmc = 1170514 | doi = 10.1093/emboj/17.6.1665 }}

Characteristics

The members of the IL-6 receptor family are 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.{{cite journal | vauthors = Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, Taga T, Kishimoto T | title = IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase | journal = Science | volume = 260 | issue = 5115 | pages = 1808–1810 | year = 1993 | pmid = 8511589 | doi = 10.1126/science.8511589 | bibcode = 1993Sci...260.1808M }} 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.{{cite journal | vauthors = Kishimoto T, Akira S, Narazaki M, Taga T | title = Interleukin-6 family of cytokines and gp130 | journal = Blood | volume = 86 | issue = 4 | pages = 1243–1254 | year = 1995 | pmid = 7632928 | doi = 10.1182/blood.V86.4.1243.bloodjournal8641243 | doi-access = free }} 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.

Inhibition of gp130

gp130 is an important part of many different types of signaling complexes. Inactivation of gp130 during development is lethal to mice.{{cite journal | vauthors = 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 WZ, Mori C, Shiota K, Yoshida N, Kishimoto T | title = Targeted disruption of gp130, a common signal transducer for the interleukin 6 family of cytokines, leads to myocardial and hematological disorders | journal = Proc. Natl. Acad. Sci. USA | volume = 93 | issue = 1 | pages = 407–411 | year = 1996 | pmid = 8552649 | pmc = 40247 | doi = 10.1073/pnas.93.1.407 | bibcode = 1996PNAS...93..407Y | doi-access = free }} 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. Loss of gp130 in the adult mouse, either globally or in a tissue-specific manner, is however increasingly linked with beneficial effects in a number of mouse models of disease.{{Cite journal |last1=Widjaja |first1=Anissa A. |last2=Cook |first2=Stuart A. |date=2024-01-23 |title=Nonspecific Inhibition of IL6 Family Cytokine Signalling by Soluble gp130 |journal=International Journal of Molecular Sciences |language=en |volume=25 |issue=3 |pages=1363 |doi=10.3390/ijms25031363 |doi-access=free |issn=1422-0067 |pmc=10855816 |pmid=38338642}} Of note, soluble gp130 (sgp130), which was thought a specific inhibitor of IL6 trans signalling, was instead found to inhibit not only IL6 signalling but also multiple other IL6-family cytokines (e.g. OSM, IL11 and CNTF). Thus the widespread benefits of sgp130 in mouse models,{{Cite journal |last1=Rose-John |first1=Stefan |last2=Jenkins |first2=Brendan J. |last3=Garbers |first3=Christoph |last4=Moll |first4=Jens M. |last5=Scheller |first5=Jürgen |date=October 2023 |title=Targeting IL-6 trans-signalling: past, present and future prospects |journal=Nature Reviews Immunology |language=en |volume=23 |issue=10 |pages=666–681 |doi=10.1038/s41577-023-00856-y |issn=1474-1733 |pmc=10108826 |pmid=37069261}} and in human trials,{{Cite journal |last1=Zhang |first1=Shenghong |last2=Chen |first2=Baili |last3=Wang |first3=Bangmao |last4=Chen |first4=Hong |last5=Li |first5=Yan |last6=Cao |first6=Qian |last7=Zhong |first7=Jie |last8=Shieh |first8=Ming-Jium |last9=Ran |first9=Zhihua |last10=Tang |first10=Tongyu |last11=Yang |first11=Ming |last12=Xu |first12=Beibei |last13=Wang |first13=Qiang |last14=Liu |first14=Yunjie |last15=Ma |first15=Lijia |date=2023-03-07 |title=Effect of Induction Therapy With Olamkicept vs Placebo on Clinical Response in Patients With Active Ulcerative Colitis: A Randomized Clinical Trial |journal=JAMA |language=en |volume=329 |issue=9 |pages=725–734 |doi=10.1001/jama.2023.1084 |issn=0098-7484 |pmc=9993185 |pmid=36881032}} may represent the benefits of global (or near global) inhibition of gp130. This suggests gp130 itself as a therapeutic target for human diseases including sepsis, systemic sclerosis, inflammatory bowel disease, among others.

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.{{cite journal | vauthors = Kishimoto T, Taga T, Akira S | title = Cytokine signal transduction | journal = Cell | volume = 76 | issue = 2 | pages = 253–262 | year = 1994 | pmid = 8293462 | doi = 10.1016/0092-8674(94)90333-6 | s2cid = 31924790 }} In particular, STAT-3 is activated which leads to the activation of many downstream genes. Other pathways activated include RAS and MAPK signaling.

Interactions

Glycoprotein 130 has been shown to interact with:

  • Grb2,{{cite journal | vauthors = Lee IS, Liu Y, Narazaki M, Hibi M, Kishimoto T, Taga T | title = Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6 | journal = FEBS Lett. | volume = 401 | issue = 2–3 | pages = 133–7 | date = January 1997 | pmid = 9013873 | doi = 10.1016/s0014-5793(96)01456-1| s2cid = 32632406 | doi-access = free | bibcode = 1997FEBSL.401..133L }}
  • HER2/neu,{{cite journal | vauthors = Grant SL, Hammacher A, Douglas AM, Goss GA, Mansfield RK, Heath JK, Begley CG | title = An unexpected biochemical and functional interaction between gp130 and the EGF receptor family in breast cancer cells | journal = Oncogene | volume = 21 | issue = 3 | pages = 460–74 | date = January 2002 | pmid = 11821958 | doi = 10.1038/sj.onc.1205100 | s2cid = 19754641 | doi-access = }}
  • Janus kinase 1{{cite journal | vauthors = Haan C, Is'harc H, Hermanns HM, Schmitz-Van De Leur H, Kerr IM, Heinrich PC, Grötzinger J, Behrmann I | title = Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction | journal = J. Biol. Chem. | volume = 276 | issue = 40 | pages = 37451–8 | date = October 2001 | pmid = 11468294 | doi = 10.1074/jbc.M106135200 | doi-access =free }}{{cite journal | vauthors = Haan C, Heinrich PC, Behrmann I | title = Structural requirements of the interleukin-6 signal transducer gp130 for its interaction with Janus kinase 1: the receptor is crucial for kinase activation | journal = Biochem. J. | volume = 361 | issue = Pt 1 | pages = 105–11 | date = January 2002 | pmid = 11742534 | pmc = 1222284 | doi = 10.1042/0264-6021:3610105}}
  • Leukemia inhibitory factor receptor,{{cite journal | vauthors = Timmermann A, Küster A, Kurth I, Heinrich PC, Müller-Newen G | title = A functional role of the membrane-proximal extracellular domains of the signal transducer gp130 in heterodimerization with the leukemia inhibitory factor receptor | journal = Eur. J. Biochem. | volume = 269 | issue = 11 | pages = 2716–26 | date = June 2002 | pmid = 12047380 | doi = 10.1046/j.1432-1033.2002.02941.x}}{{cite journal | vauthors = Mosley B, De Imus C, Friend D, Boiani N, Thoma B, Park LS, Cosman D | title = Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation | journal = J. Biol. Chem. | volume = 271 | issue = 51 | pages = 32635–43 | date = December 1996 | pmid = 8999038 | doi = 10.1074/jbc.271.51.32635| doi-access = free }}
  • PTPN11,{{cite journal | vauthors = Kim H, Baumann H | title = Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells | journal = J. Biol. Chem. | volume = 272 | issue = 49 | pages = 30741–7 | date = December 1997 | pmid = 9388212 | doi = 10.1074/jbc.272.49.30741| doi-access = free }}{{cite journal | vauthors = Anhuf D, Weissenbach M, Schmitz J, Sobota R, Hermanns HM, Radtke S, Linnemann S, Behrmann I, Heinrich PC, Schaper F | title = Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation | journal = J. Immunol. | volume = 165 | issue = 5 | pages = 2535–43 | date = September 2000 | pmid = 10946280 | doi = 10.4049/jimmunol.165.5.2535| doi-access = free }}
  • SHC1,{{cite journal | vauthors = Giordano V, De Falco G, Chiari R, Quinto I, Pelicci PG, Bartholomew L, Delmastro P, Gadina M, Scala G | title = Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase | journal = J. Immunol. | volume = 158 | issue = 9 | pages = 4097–103 | date = May 1997 | doi = 10.4049/jimmunol.158.9.4097 | pmid = 9126968 | s2cid = 44339682 | doi-access = free }}
  • SOCS3,{{cite journal | vauthors = Lehmann U, Schmitz J, Weissenbach M, Sobota RM, Hortner M, Friederichs K, Behrmann I, Tsiaris W, Sasaki A, Schneider-Mergener J, Yoshimura A, Neel BG, Heinrich PC, Schaper F | title = SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130 | journal = J. Biol. Chem. | volume = 278 | issue = 1 | pages = 661–71 | date = January 2003 | pmid = 12403768 | doi = 10.1074/jbc.M210552200 | doi-access = free }} and
  • TLE1.{{cite journal | vauthors = Liu F, Liu Y, Li D, Zhu Y, Ouyang W, Xie X, Jin B | title = The transcription co-repressor TLE1 interacted with the intracellular region of gpl30 through its Q domain | journal = Mol. Cell. Biochem. | volume = 232 | issue = 1–2 | pages = 163–7 | date = March 2002 | pmid = 12030375 | doi = 10.1023/A:1014880813692| s2cid = 8270300 }}

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References

{{Reflist|35em}}

Further reading

{{refbegin|35em}}

  • {{cite journal | vauthors = Ip NY, Nye SH, Boulton TG, Davis S, Taga T, Li Y, Birren SJ, Yasukawa K, Kishimoto T, Anderson DJ | title = CNTF and LIF act on neuronal cells via shared signaling pathways that involve the IL-6 signal transducing receptor component gp130 | journal = Cell | volume = 69 | issue = 7 | pages = 1121–32 | year = 1992 | pmid = 1617725 | doi = 10.1016/0092-8674(92)90634-O | s2cid = 45816061 }}
  • {{cite journal | vauthors = Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T | title = Molecular cloning and expression of an IL-6 signal transducer, gp130 | journal = Cell | volume = 63 | issue = 6 | pages = 1149–57 | year = 1991 | pmid = 2261637 | doi = 10.1016/0092-8674(90)90411-7 | s2cid = 30852638 }}
  • {{cite journal | vauthors = Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirano T, Kishimoto T | title = Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130 | journal = Cell | volume = 58 | issue = 3 | pages = 573–81 | year = 1989 | pmid = 2788034 | doi = 10.1016/0092-8674(89)90438-8 | s2cid = 41245022 }}
  • {{cite journal | vauthors = Rodriguez C, Grosgeorge J, Nguyen VC, Gaudray P, Theillet C | title = Human gp130 transducer chain gene (IL6ST) is localized to chromosome band 5q11 and possesses a pseudogene on chromosome band 17p11 | journal = Cytogenet. Cell Genet. | volume = 70 | issue = 1–2 | pages = 64–7 | year = 1995 | pmid = 7736792 | doi = 10.1159/000133993 }}
  • {{cite journal | vauthors = Narazaki M, Yasukawa K, Saito T, Ohsugi Y, Fukui H, Koishihara Y, Yancopoulos GD, Taga T, Kishimoto T | title = Soluble forms of the interleukin-6 signal-transducing receptor component gp130 in human serum possessing a potential to inhibit signals through membrane-anchored gp130 | journal = Blood | volume = 82 | issue = 4 | pages = 1120–6 | year = 1993 | pmid = 8353278 | doi = 10.1182/blood.V82.4.1120.1120| doi-access = free }}
  • {{cite journal | vauthors = Davis S, Aldrich TH, Stahl N, Pan L, Taga T, Kishimoto T, Ip NY, Yancopoulos GD | title = LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor | journal = Science | volume = 260 | issue = 5115 | pages = 1805–8 | year = 1993 | pmid = 8390097 | doi = 10.1126/science.8390097 | bibcode = 1993Sci...260.1805D }}
  • {{cite journal | vauthors = Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, Taga T, Kishimoto T | title = IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase | journal = Science | volume = 260 | issue = 5115 | pages = 1808–10 | year = 1993 | pmid = 8511589 | doi = 10.1126/science.8511589 | bibcode = 1993Sci...260.1808M }}
  • {{cite journal | vauthors = Sharkey AM, Dellow K, Blayney M, Macnamee M, Charnock-Jones S, Smith SK | title = Stage-specific expression of cytokine and receptor messenger ribonucleic acids in human preimplantation embryos | journal = Biol. Reprod. | volume = 53 | issue = 4 | pages = 974–81 | year = 1996 | pmid = 8547494 | doi = 10.1095/biolreprod53.4.974 | doi-access = free }}
  • {{cite journal | vauthors = Mosley B, De Imus C, Friend D, Boiani N, Thoma B, Park LS, Cosman D | title = Dual oncostatin M (OSM) receptors. Cloning and characterization of an alternative signaling subunit conferring OSM-specific receptor activation | journal = J. Biol. Chem. | volume = 271 | issue = 51 | pages = 32635–43 | year = 1997 | pmid = 8999038 | doi = 10.1074/jbc.271.51.32635 | doi-access = free }}
  • {{cite journal | vauthors = Lee IS, Liu Y, Narazaki M, Hibi M, Kishimoto T, Taga T | title = Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6 | journal = FEBS Lett. | volume = 401 | issue = 2–3 | pages = 133–7 | year = 1997 | pmid = 9013873 | doi = 10.1016/S0014-5793(96)01456-1 | s2cid = 32632406 | doi-access = free | bibcode = 1997FEBSL.401..133L }}
  • {{cite journal | vauthors = Auguste P, Guillet C, Fourcin M, Olivier C, Veziers J, Pouplard-Barthelaix A, Gascan H | title = Signaling of type II oncostatin M receptor | journal = J. Biol. Chem. | volume = 272 | issue = 25 | pages = 15760–4 | year = 1997 | pmid = 9188471 | doi = 10.1074/jbc.272.25.15760 | doi-access = free }}
  • {{cite journal | vauthors = Schiemann WP, Bartoe JL, Nathanson NM | title = 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 | journal = J. Biol. Chem. | volume = 272 | issue = 26 | pages = 16631–6 | year = 1997 | pmid = 9195977 | doi = 10.1074/jbc.272.26.16631 | doi-access = free }}
  • {{cite journal | vauthors = Diamant M, Rieneck K, Mechti N, Zhang XG, Svenson M, Bendtzen K, Klein B | title = Cloning and expression of an alternatively spliced mRNA encoding a soluble form of the human interleukin-6 signal transducer gp130 | journal = FEBS Lett. | volume = 412 | issue = 2 | pages = 379–84 | year = 1997 | pmid = 9256256 | doi = 10.1016/S0014-5793(97)00750-3 | s2cid = 12420499 | doi-access = free }}
  • {{cite journal | vauthors = Koshelnick Y, Ehart M, Hufnagl P, Heinrich PC, Binder BR | title = 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 | journal = J. Biol. Chem. | volume = 272 | issue = 45 | pages = 28563–7 | year = 1997 | pmid = 9353320 | doi = 10.1074/jbc.272.45.28563 | doi-access = free }}
  • {{cite journal | vauthors = Kim H, Baumann H | title = Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells | journal = J. Biol. Chem. | volume = 272 | issue = 49 | pages = 30741–7 | year = 1998 | pmid = 9388212 | doi = 10.1074/jbc.272.49.30741 | doi-access = free }}
  • {{cite journal | vauthors = Bravo J, Staunton D, Heath JK, Jones EY | title = Crystal structure of a cytokine-binding region of gp130 | journal = EMBO J. | volume = 17 | issue = 6 | pages = 1665–74 | year = 1998 | pmid = 9501088 | pmc = 1170514 | doi = 10.1093/emboj/17.6.1665 }}
  • {{cite journal | vauthors = Barton VA, Hudson KR, Heath JK | title = Identification of three distinct receptor binding sites of murine interleukin-11 | journal = J. Biol. Chem. | volume = 274 | issue = 9 | pages = 5755–61 | year = 1999 | pmid = 10026196 | doi = 10.1074/jbc.274.9.5755 | doi-access = free }}
  • {{cite journal | vauthors = Hirota H, Chen J, Betz UA, Rajewsky K, Gu Y, Ross J, Müller W, Chien KR | title = Loss of a gp130 cardiac muscle cell survival pathway is a critical event in the onset of heart failure during biomechanical stress | journal = Cell | volume = 97 | issue = 2 | pages = 189–98 | year = 1999 | pmid = 10219240 | doi = 10.1016/S0092-8674(00)80729-1 | s2cid = 17955799 | doi-access = free }}
  • {{cite journal | vauthors = Tacken I, Dahmen H, Boisteau O, Minvielle S, Jacques Y, Grötzinger J, Küster A, Horsten U, Blanc C, Montero-Julian FA, Heinrich PC, Müller-Newen G | title = Definition of receptor binding sites on human interleukin-11 by molecular modeling-guided mutagenesis | journal = Eur. J. Biochem. | volume = 265 | issue = 2 | pages = 645–55 | year = 1999 | pmid = 10504396 | doi = 10.1046/j.1432-1327.1999.00755.x | doi-access = free }}
  • {{cite journal | vauthors = Chung TD, Yu JJ, Kong TA, Spiotto MT, Lin JM | title = Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines | journal = Prostate | volume = 42 | issue = 1 | pages = 1–7 | year = 2000 | pmid = 10579793 | doi = 10.1002/(SICI)1097-0045(20000101)42:1<1::AID-PROS1>3.0.CO;2-Y | s2cid = 86404104 }}

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External links

  • {{MeshName|Cytokine+Receptor+gp130}}

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{{Interleukin receptor modulators}}

Category:Glycoproteins

Category:Type I cytokine receptors