Glycoprotein 130

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This article is about the glycoprotein. For the stimulant drug, see G-130.

Template:PBB 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

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.

Interactions

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]

References

  1. ^ Hibi; Murakami, M; Saito, M; Hirano, T; Taga, T; Kishimoto, T; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help)
  2. ^ Bravo; Staunton, D; Heath, JK; Jones, EY; et al. (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. {{cite journal}}: Explicit use of et al. in: |author= (help)
  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. doi:10.1126/science.8511589. PMID 8511589.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  4. ^ Kishimoto T, Akira S, Narazaki M, Taga T (1995). "Interleukin-6 family of cytokines and gp130". Blood. 86 (4): 1243–1254. PMID 7632928.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  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. doi:10.1073/pnas.93.1.407. PMC 40247. PMID 8552649.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  6. ^ 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.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Liu, Fei (March 2002). "The transcription co-repressor TLE1 interacted with the intracellular region of gpl30 through its Q domain". Mol. Cell. Biochem. 232 (1–2). Netherlands: 163–7. doi:10.1023/A:1014880813692. ISSN 0300-8177. PMID 12030375. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  8. ^ a b Lehmann, Ute (January 2003). "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130". J. Biol. Chem. 278 (1). United States: 661–71. doi:10.1074/jbc.M210552200. ISSN 0021-9258. PMID 12403768. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: unflagged free DOI (link)
  9. ^ Grant, Susan L (January 2002). "An unexpected biochemical and functional interaction between gp130 and the EGF receptor family in breast cancer cells". Oncogene. 21 (3). England: 460–74. doi:10.1038/sj.onc.1205100. ISSN 0950-9232. PMID 11821958. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  10. ^ Anhuf, D (September 2000). "Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation". J. Immunol. 165 (5). UNITED STATES: 2535–43. ISSN 0022-1767. PMID 10946280. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  11. ^ a b Kim, H (December 1997). "Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells". J. Biol. Chem. 272 (49). UNITED STATES: 30741–7. doi:10.1074/jbc.272.49.30741. ISSN 0021-9258. PMID 9388212. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: unflagged free DOI (link)
  12. ^ Timmermann, Andreas (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). Germany: 2716–26. doi:10.1046/j.1432-1033.2002.02941.x. ISSN 0014-2956. PMID 12047380. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  13. ^ Mosley, B (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). UNITED STATES: 32635–43. doi:10.1074/jbc.271.51.32635. ISSN 0021-9258. PMID 8999038. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: unflagged free DOI (link)
  14. ^ Lee, I S (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). NETHERLANDS: 133–7. doi:10.1016/S0014-5793(96)01456-1. ISSN 0014-5793. PMID 9013873. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  15. ^ Haan, C (October 2001). "Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction". J. Biol. Chem. 276 (40). United States: 37451–8. doi:10.1074/jbc.M106135200. ISSN 0021-9258. PMID 11468294. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)CS1 maint: unflagged free DOI (link)
  16. ^ Haan, Claude (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). England: 105–11. doi:10.1042/0264-6021:3610105. ISSN 0264-6021. PMC 1222284. PMID 11742534. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  17. ^ Giordano, V (May 1997). "Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase". J. Immunol. 158 (9). UNITED STATES: 4097–103. ISSN 0022-1767. PMID 9126968. {{cite journal}}: Cite has empty unknown parameters: |laydate=, |laysummary=, and |laysource= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)

Further reading

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