The members of theIL-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 thenhomodimerizes to form ahexameric complex which can produce downstream signals.[7] There are many other proteins which associate with gp130, such ascardiotrophin 1 (CT-1),leukemia inhibitory factor (LIF),ciliary neurotrophic factor (CNTF),oncostatin M (OSM), andIL-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 includeLIF-R,OSM-R, andG-CSF-R.
gp130 is an important part of many different types of signaling complexes. Inactivation of gp130 during development is lethal to mice.[9]Homozygous mice who are born show a number of defects including impaired development of theventricularmyocardium.Haematopoietic effects included reduced numbers ofstem cells in thespleen andliver. 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.[10] 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).[10] Thus the widespread benefits of sgp130 in mouse models,[11] and in human trials,[12] 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.
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T (Dec 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.PMID2261637.S2CID30852638.
^Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, et al. (Jun 1993). "IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase".Science.260 (5115). New York, N.Y.:1808–1810.Bibcode:1993Sci...260.1808M.doi:10.1126/science.8511589.PMID8511589.
^Grant SL, Hammacher A, Douglas AM, Goss GA, Mansfield RK, Heath JK, et al. (January 2002). "An unexpected biochemical and functional interaction between gp130 and the EGF receptor family in breast cancer cells".Oncogene.21 (3):460–474.doi:10.1038/sj.onc.1205100.PMID11821958.S2CID19754641.
^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".European Journal of Biochemistry.269 (11):2716–2726.doi:10.1046/j.1432-1033.2002.02941.x.PMID12047380.
^Liu F, Liu Y, Li D, Zhu Y, Ouyang W, Xie X, et al. (March 2002). "The transcription co-repressor TLE1 interacted with the intracellular region of gpl30 through its Q domain".Molecular and Cellular Biochemistry.232 (1–2):163–167.doi:10.1023/A:1014880813692.PMID12030375.S2CID8270300.
Ip NY, Nye SH, Boulton TG, Davis S, Taga T, Li Y, et al. (Jun 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):1121–1132.doi:10.1016/0092-8674(92)90634-O.PMID1617725.S2CID45816061.
Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T (Dec 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.PMID2261637.S2CID30852638.
Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, et al. (Aug 1989). "Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130".Cell.58 (3):573–581.doi:10.1016/0092-8674(89)90438-8.PMID2788034.S2CID41245022.
Rodriguez C, Grosgeorge J, Nguyen VC, Gaudray P, Theillet C (1995). "Human gp130 transducer chain gene (IL6ST) is localized to chromosome band 5q11 and possesses a pseudogene on chromosome band 17p11".Cytogenetics and Cell Genetics.70 (1–2):64–67.doi:10.1159/000133993.PMID7736792.
Davis S, Aldrich TH, Stahl N, Pan L, Taga T, Kishimoto T, et al. (Jun 1993). "LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor".Science.260 (5115). New York, N.Y.:1805–1808.Bibcode:1993Sci...260.1805D.doi:10.1126/science.8390097.PMID8390097.
Murakami M, Hibi M, Nakagawa N, Nakagawa T, Yasukawa K, Yamanishi K, et al. (Jun 1993). "IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase".Science.260 (5115). New York, N.Y.:1808–1810.Bibcode:1993Sci...260.1808M.doi:10.1126/science.8511589.PMID8511589.
