Glycoprotein 130

Last updated
IL6ST
GP130 Crystal Structure.rsh.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases IL6ST , CD130, CDW130, GP130, IL-6RB, interleukin 6 signal transducer
External IDs OMIM: 600694 MGI: 96560 HomoloGene: 1645 GeneCards: IL6ST
Orthologs
SpeciesHumanMouse
Entrez

3572

16195

Ensembl

ENSG00000134352

ENSMUSG00000021756

UniProt

P40189
Q17RA0

Q00560

RefSeq (mRNA)

NM_001190981
NM_002184
NM_175767

NM_010560

RefSeq (protein)

NP_034690

Location (UCSC) Chr 5: 55.94 – 55.99 Mb Chr 13: 112.6 – 112.65 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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. [5] [6]

Characteristics

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. [7] 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. [8] 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. [9] 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. [10] 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:

Related Research Articles

<span class="mw-page-title-main">Leukemia inhibitory factor</span> Mammalian protein found in Homo sapiens

Leukemia inhibitory factor, or LIF, is an interleukin 6 class cytokine that affects cell growth by inhibiting differentiation. When LIF levels drop, the cells differentiate.

<span class="mw-page-title-main">Oncostatin M</span> Mammalian protein found in Homo sapiens

Oncostatin M, also known as OSM, is a protein that in humans is encoded by the OSM gene.

<span class="mw-page-title-main">Interleukin 11</span> Protein-coding gene in the species Homo sapiens

Interleukin 11 is a protein that in humans is encoded by the IL11 gene.

Type I cytokine receptors are transmembrane receptors expressed on the surface of cells that recognize and respond to cytokines with four α-helical strands. These receptors are also known under the name hemopoietin receptors, and share a common amino acid motif (WSXWS) in the extracellular portion adjacent to the cell membrane. Members of the type I cytokine receptor family comprise different chains, some of which are involved in ligand/cytokine interaction and others that are involved in signal transduction.

<span class="mw-page-title-main">TRAF6</span> Protein-coding gene in the species Homo sapiens

TRAF6 is a TRAF human protein.

<span class="mw-page-title-main">Oncostatin M receptor</span> Protein-coding gene in the species Homo sapiens

Oncostatin-M specific receptor subunit beta also known as the Oncostatin M receptor (OSMR), is one of the receptor proteins for oncostatin M, that in humans is encoded by the OSMR gene.

<span class="mw-page-title-main">Leukemia inhibitory factor receptor</span> Polyfunctional cytokine

LIFR also known as CD118, is a subunit of a receptor for leukemia inhibitory factor.

<span class="mw-page-title-main">Janus kinase 2</span> Non-receptor tyrosine kinase and coding gene in humans

Janus kinase 2 is a non-receptor tyrosine kinase. It is a member of the Janus kinase family and has been implicated in signaling by members of the type II cytokine receptor family, the GM-CSF receptor family, the gp130 receptor family, and the single chain receptors.

<span class="mw-page-title-main">Janus kinase 1</span>

JAK1 is a human tyrosine kinase protein essential for signaling for certain type I and type II cytokines. It interacts with the common gamma chain (γc) of type I cytokine receptors, to elicit signals from the IL-2 receptor family, the IL-4 receptor family, the gp130 receptor family. It is also important for transducing a signal by type I (IFN-α/β) and type II (IFN-γ) interferons, and members of the IL-10 family via type II cytokine receptors. Jak1 plays a critical role in initiating responses to multiple major cytokine receptor families. Loss of Jak1 is lethal in neonatal mice, possibly due to difficulties suckling. Expression of JAK1 in cancer cells enables individual cells to contract, potentially allowing them to escape their tumor and metastasize to other parts of the body.

<span class="mw-page-title-main">MAPK1</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 1, also known as ERK2, is an enzyme that in humans is encoded by the MAPK1 gene.

<span class="mw-page-title-main">MAPK8</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 8 is a ubiquitous enzyme that in humans is encoded by the MAPK8 gene.

<span class="mw-page-title-main">SOCS3</span> Protein

Suppressor of cytokine signaling 3 is a protein that in humans is encoded by the SOCS3 gene. This gene encodes a member of the STAT-induced STAT inhibitor (SSI), also known as suppressor of cytokine signaling (SOCS), family. SSI family members are cytokine-inducible negative regulators of cytokine signaling.

<span class="mw-page-title-main">MAP3K7</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 7 (MAP3K7), also known as TAK1, is an enzyme that in humans is encoded by the MAP3K7 gene.

<span class="mw-page-title-main">IRS2</span> Protein-coding gene in the species Homo sapiens

Insulin receptor substrate 2 is a protein that in humans is encoded by the IRS2 gene.

<span class="mw-page-title-main">Interleukin-6 receptor</span> Protein-coding gene in the species Homo sapiens

Interleukin 6 receptor (IL6R) also known as CD126 is a type I cytokine receptor.

<span class="mw-page-title-main">STAT5A</span> Protein-coding gene in the species Homo sapiens

Signal transducer and activator of transcription 5A is a protein that in humans is encoded by the STAT5A gene. STAT5A orthologs have been identified in several placentals for which complete genome data are available.

<span class="mw-page-title-main">Interleukin 1 receptor, type I</span>

Interleukin 1 receptor, type I (IL1R1) also known as CD121a, is an interleukin receptor. IL1R1 also denotes its human gene.

<span class="mw-page-title-main">TAB1</span> Protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase kinase kinase 7-interacting protein 1 is an enzyme that in humans is encoded by the TAB1 gene.

<span class="mw-page-title-main">IL31RA</span> Protein-coding gene in the species Homo sapiens

Interleukin-31 receptor A is a protein that in humans is encoded by the IL31RA gene.

<span class="mw-page-title-main">STAT5B</span> Protein-coding gene in the species Homo sapiens

Signal transducer and activator of transcription 5B is a protein that in humans is encoded by the STAT5B gene. STAT5B orthologs have been identified in most placentals for which complete genome data are available.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000134352 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021756 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Hibi M, 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. doi:10.1016/0092-8674(90)90411-7. PMID   2261637. S2CID   30852638.
  6. ↑ Bravo J, Staunton D, Heath JK, Jones EY (1998). "Crystal structure of a cytokine-binding region of gp130". EMBO J. 17 (6): 1665–1674. doi:10.1093/emboj/17.6.1665. PMC   1170514 . PMID   9501088.
  7. ↑ 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. Bibcode:1993Sci...260.1808M. doi:10.1126/science.8511589. PMID   8511589.
  8. ↑ Kishimoto T, Akira S, Narazaki M, Taga T (1995). "Interleukin-6 family of cytokines and gp130". Blood. 86 (4): 1243–1254. doi: 10.1182/blood.V86.4.1243.bloodjournal8641243 . PMID   7632928.
  9. ↑ 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 (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. Bibcode:1996PNAS...93..407Y. doi: 10.1073/pnas.93.1.407 . PMC   40247 . PMID   8552649.
  10. ↑ Kishimoto T, Taga T, Akira S (1994). "Cytokine signal transduction". Cell. 76 (2): 253–262. doi:10.1016/0092-8674(94)90333-6. PMID   8293462. S2CID   31924790.
  11. ↑ Lee IS, 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. 401 (2–3): 133–7. doi: 10.1016/s0014-5793(96)01456-1 . PMID   9013873. S2CID   32632406.
  12. ↑ Grant SL, Hammacher A, Douglas AM, Goss GA, Mansfield RK, Heath JK, Begley CG (January 2002). "An unexpected biochemical and functional interaction between gp130 and the EGF receptor family in breast cancer cells". Oncogene. 21 (3): 460–74. doi:10.1038/sj.onc.1205100. PMID   11821958. S2CID   19754641.
  13. 1 2 Kim H, Baumann H (December 1997). "Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells". J. Biol. Chem. 272 (49): 30741–7. doi: 10.1074/jbc.272.49.30741 . PMID   9388212.
  14. ↑ Haan C, Is'harc H, Hermanns HM, Schmitz-Van De Leur H, Kerr IM, Heinrich PC, Grötzinger J, Behrmann I (October 2001). "Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction". J. Biol. Chem. 276 (40): 37451–8. doi: 10.1074/jbc.M106135200 . PMID   11468294.
  15. ↑ Haan C, Heinrich PC, Behrmann I (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. 361 (Pt 1): 105–11. doi:10.1042/0264-6021:3610105. PMC   1222284 . PMID   11742534.
  16. ↑ Timmermann A, Küster A, Kurth I, Heinrich PC, Müller-Newen G (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. 269 (11): 2716–26. doi:10.1046/j.1432-1033.2002.02941.x. PMID   12047380.
  17. ↑ Mosley B, De Imus C, Friend D, Boiani N, Thoma B, Park LS, 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. 271 (51): 32635–43. doi: 10.1074/jbc.271.51.32635 . PMID   8999038.
  18. 1 2 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 (January 2003). "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130". J. Biol. Chem. 278 (1): 661–71. doi: 10.1074/jbc.M210552200 . PMID   12403768.
  19. ↑ Anhuf D, Weissenbach M, Schmitz J, Sobota R, Hermanns HM, Radtke S, Linnemann S, Behrmann I, Heinrich PC, Schaper F (September 2000). "Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation". J. Immunol. 165 (5): 2535–43. doi: 10.4049/jimmunol.165.5.2535 . PMID   10946280.
  20. ↑ Giordano V, De Falco G, Chiari R, Quinto I, Pelicci PG, Bartholomew L, Delmastro P, Gadina M, Scala G (May 1997). "Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase". J. Immunol. 158 (9): 4097–103. doi: 10.4049/jimmunol.158.9.4097 . PMID   9126968. S2CID   44339682.
  21. ↑ Liu F, Liu Y, Li D, Zhu Y, Ouyang W, Xie X, Jin B (March 2002). "The transcription co-repressor TLE1 interacted with the intracellular region of gpl30 through its Q domain". Mol. Cell. Biochem. 232 (1–2): 163–7. doi:10.1023/A:1014880813692. PMID   12030375. S2CID   8270300.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.