Biology:Glycoprotein 130
 Generic protein structure example |
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.[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:
- Grb2,[7]
- HER2/neu,[8]
- Janus kinase 1[9][10][11]
- Leukemia inhibitory factor receptor,[12][13]
- PTPN11,[9][14][15]
- SHC1,[16]
- SOCS3,[14] and
- TLE1.[17]
References
- ↑ "Molecular cloning and expression of an IL-6 signal transducer, gp130". Cell 63 (6): 1149–1157. 1990. doi:10.1016/0092-8674(90)90411-7. PMID 2261637.
- ↑ "Crystal structure of a cytokine-binding region of gp130". EMBO J 17 (6): 1665–1674. 1998. doi:10.1093/emboj/17.6.1665. PMID 9501088.
- ↑ "IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase". Science 260 (5115): 1808–1810. 1993. doi:10.1126/science.8511589. PMID 8511589. Bibcode: 1993Sci...260.1808M.
- ↑ "Interleukin-6 family of cytokines and gp130". Blood 86 (4): 1243–1254. 1995. doi:10.1182/blood.V86.4.1243.bloodjournal8641243. PMID 7632928.
- ↑ "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. 1996. doi:10.1073/pnas.93.1.407. PMID 8552649. Bibcode: 1996PNAS...93..407Y.
- ↑ "Cytokine signal transduction". Cell 76 (2): 253–262. 1994. doi:10.1016/0092-8674(94)90333-6. PMID 8293462.
- ↑ "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. January 1997. doi:10.1016/s0014-5793(96)01456-1. PMID 9013873.
- ↑ "An unexpected biochemical and functional interaction between gp130 and the EGF receptor family in breast cancer cells". Oncogene 21 (3): 460–74. January 2002. doi:10.1038/sj.onc.1205100. PMID 11821958.
- ↑ 9.0 9.1 "Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells". J. Biol. Chem. 272 (49): 30741–7. December 1997. doi:10.1074/jbc.272.49.30741. PMID 9388212.
- ↑ "Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction". J. Biol. Chem. 276 (40): 37451–8. October 2001. doi:10.1074/jbc.M106135200. PMID 11468294.
- ↑ "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. January 2002. doi:10.1042/0264-6021:3610105. PMID 11742534.
- ↑ "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. June 2002. doi:10.1046/j.1432-1033.2002.02941.x. PMID 12047380.
- ↑ "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. December 1996. doi:10.1074/jbc.271.51.32635. PMID 8999038.
- ↑ 14.0 14.1 "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130". J. Biol. Chem. 278 (1): 661–71. January 2003. doi:10.1074/jbc.M210552200. PMID 12403768.
- ↑ "Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation". J. Immunol. 165 (5): 2535–43. September 2000. doi:10.4049/jimmunol.165.5.2535. PMID 10946280.
- ↑ "Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase". J. Immunol. 158 (9): 4097–103. May 1997. doi:10.4049/jimmunol.158.9.4097. PMID 9126968.
- ↑ "The transcription co-repressor TLE1 interacted with the intracellular region of gpl30 through its Q domain". Mol. Cell. Biochem. 232 (1–2): 163–7. March 2002. doi:10.1023/A:1014880813692. PMID 12030375.
Further reading
- "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. 1992. doi:10.1016/0092-8674(92)90634-O. PMID 1617725.
- "Molecular cloning and expression of an IL-6 signal transducer, gp130". Cell 63 (6): 1149–57. 1991. doi:10.1016/0092-8674(90)90411-7. PMID 2261637.
- "Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130". Cell 58 (3): 573–81. 1989. doi:10.1016/0092-8674(89)90438-8. PMID 2788034.
- "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. 1995. doi:10.1159/000133993. PMID 7736792.
- "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. 1993. doi:10.1182/blood.V82.4.1120.1120. PMID 8353278.
- "LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor". Science 260 (5115): 1805–8. 1993. doi:10.1126/science.8390097. PMID 8390097. Bibcode: 1993Sci...260.1805D.
- "IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase". Science 260 (5115): 1808–10. 1993. doi:10.1126/science.8511589. PMID 8511589. Bibcode: 1993Sci...260.1808M.
- "Stage-specific expression of cytokine and receptor messenger ribonucleic acids in human preimplantation embryos". Biol. Reprod. 53 (4): 974–81. 1996. doi:10.1095/biolreprod53.4.974. PMID 8547494.
- "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. 1997. doi:10.1074/jbc.271.51.32635. PMID 8999038.
- "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. 1997. doi:10.1016/S0014-5793(96)01456-1. PMID 9013873.
- "Signaling of type II oncostatin M receptor". J. Biol. Chem. 272 (25): 15760–4. 1997. doi:10.1074/jbc.272.25.15760. PMID 9188471.
- "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. 1997. doi:10.1074/jbc.272.26.16631. PMID 9195977.
- "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. 1997. doi:10.1016/S0014-5793(97)00750-3. PMID 9256256.
- "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. 1997. doi:10.1074/jbc.272.45.28563. PMID 9353320.
- "Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells". J. Biol. Chem. 272 (49): 30741–7. 1998. doi:10.1074/jbc.272.49.30741. PMID 9388212.
- "Crystal structure of a cytokine-binding region of gp130". EMBO J. 17 (6): 1665–74. 1998. doi:10.1093/emboj/17.6.1665. PMID 9501088.
- "Identification of three distinct receptor binding sites of murine interleukin-11". J. Biol. Chem. 274 (9): 5755–61. 1999. doi:10.1074/jbc.274.9.5755. PMID 10026196.
- "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. 1999. doi:10.1016/S0092-8674(00)80729-1. PMID 10219240.
- "Definition of receptor binding sites on human interleukin-11 by molecular modeling-guided mutagenesis". Eur. J. Biochem. 265 (2): 645–55. 1999. doi:10.1046/j.1432-1327.1999.00755.x. PMID 10504396.
- "Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines". Prostate 42 (1): 1–7. 2000. doi:10.1002/(SICI)1097-0045(20000101)42:1<1::AID-PROS1>3.0.CO;2-Y. PMID 10579793.
External links
- Cytokine+Receptor+gp130 at the US National Library of Medicine Medical Subject Headings (MeSH)
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