Glikoprotein 130

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Interleukin 6 signal transducer (gp130, onkostatin M receptor)

Kristalna struktura Gp130 ekstracelularnog domaina (1p9m).
Dostupne strukture
1bj8, 1bqu, 1i1r, 1p9m, 1pvh
Identifikatori
SimboliIL6ST; CD130; CDw130; GP130; GP130-RAPS; IL6R-beta
Vanjski IDOMIM: 600694 MGI: 96560 HomoloGene: 1645 GeneCards: IL6ST Gene
Ortolozi
VrstaČovekMiš
Entrez357216195
EnsemblENSG00000134352ENSMUSG00000021756
UniProtP40189Q3TDT5
RefSeq (mRNA)NM_002184NM_010560
RefSeq (protein)NP_002175NP_034690
Lokacija (UCSC)Chr 5:
55.23 - 55.29 Mb		Chr 13:
113.58 - 113.63 Mb
PubMed pretraga[1][2]

Glikoprotein 130 (takođe poznat kao gp130, IL6ST, IL6-beta ili CD130) je transmembranski protein. On je osnivački član klase citokinskih receptora. On formira jednu podjedinicu tipa I citokinskih receptora u IL-6 receptorskoj familiji. On se često naziva zajedničkom gp130 podjedinicom, i važan je za signal transdukciju nakon interakcije sa citokinom. Kao i drugi citokinski receptori tipa I, gp130 poseduje WSXWS aminokiselinski motiv koji osigurava korektno proteinsko savijanje i vezivanje liganda. On interaguje sa Janus kinazom da bi izazvao intracelularni signal nakon interakcije receptora sa ligandom. Strukturno, gp130 se sastoji od pet fibronektin tip-III domena i jednog imunoglobulinu-sličnog C2-tipa domena na njegovom ekstracelularnom delu.[1][2]

Karakteristike

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Svi članovi IL-6 receptorske familije formiraju kompleks sa gp130 proteinom, i putem njega prenose signal. Na primer, IL-6 se veže za IL-6 receptor. Kompleks ova dva proteina se onda asocira sa gp130. Taj kompleks od 3 proteina se homodimerizuje da formira heksamerni kompleks koji može da proizvede nizvodne signale.[3] Postoje mnogi drugi proteini koji se asociraju sa gp130, kao što su kardiotrofin 1 (CT-1), inhibitorni faktor leukemije (LIF), cilijarni neurotrofni faktor (CNTF), onkostatin M (OSM), i IL-11.[4] Postoji takođe nekoliko drugih proteina koji imaju strukturnu sličnost sa gp130, sadrže WSXWS motiv i očuvane cisteinske ostatke. Članovi ove grupe su: LIF-R, OSM-R, i G-CSF-R.

Gubitak gp130

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gp130 je važan deo mnogih različitih tipova signalnih kompleksa. Inaktivacija gp130 proteina je letalna kod miševa.[5] Homozigotni miševi nakon rođenja ispoljavaju brojne defekte, jedan od kojih je poremećeni razvoj ventrikularnih miokardijuma. Hematopoetski efekti obuhvataju redukovanje brojeva stem ćelija u slezini i jetri.

Prenos signala

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gp130 nema unutrašnju tirozin kinaznu aktivnost. Umesto toga, on je fosforilisan na tirozin ostacima nakon kompleksiranja sa drugim proteinima. Fosforilacija dovodi do asocijacije sa JAK/Tyk tirozin kinazama i STAT proteinskim transkripcionim faktorima[6] Specifično, STAT-3 se aktivira, što dovodi do aktivacije mnogih nizvodnih gena. Drugi putevi aktivacije su RAS i MAPK signalizacija.

Interakcije

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Za glikoprotein 130 je bilo pokazano interaguje sa TLE1,[7] SOCS3,[8] HER2/neu,[9] PTPN11,[8][10][11] Leukemijski inhibitorni faktor receptorom,[12][13] Grb2,[14] Janus kinaza 1[15][11][16] i SHC1.[17]

Reference

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  1. ↑ Hibi et al.; 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. 
  2. ↑ Bravo et al.; 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. 
  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. 
  4. ↑ Kishimoto T, Akira S, Narazaki M, Taga T (1995). „Interleukin-6 family of cytokines and gp130”. Blood 86 (4): 1243–1254. PMID 7632928. 
  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 IL-6-family of cytokines, leads to myocardial and hematological disorders”. Proc Natl Acad Sci 93 (1): 407–411. DOI:10.1073/pnas.93.1.407. PMC 40247. PMID 8552649. 
  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. 
  7. ↑ Liu, Fei; Liu Yin, Li Demin, Zhu Yong, Ouyang Weiming, Xie Xin, Jin Boquan (March 2002). „The transcription co-repressor TLE1 interacted with the intracellular region of gpl30 through its Q domain”. Mol. Cell. Biochem. (Netherlands) 232 (1-2): 163–7. DOI:10.1023/A:1014880813692. ISSN 0300-8177. PMID 12030375. 
  8. ↑ 8,0 8,1 Lehmann, Ute; Schmitz Jochen, Weissenbach Manuela, Sobota Radoslaw M, Hortner Michael, Friederichs Kerstin, Behrmann Iris, Tsiaris William, Sasaki Atsuo, Schneider-Mergener Jens, Yoshimura Akihiko, Neel Benjamin G, Heinrich Peter C, Schaper Fred (January 2003). „SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130”. J. Biol. Chem. (United States) 278 (1): 661–71. DOI:10.1074/jbc.M210552200. ISSN 0021-9258. PMID 12403768. 
  9. ↑ Grant, Susan L; Hammacher Annet, Douglas Andrea M, Goss Geraldine A, Mansfield Rachel K, Heath John K, Begley C Glenn (January 2002). „An unexpected biochemical and functional interaction between gp130 and the EGF receptor family in breast cancer cells”. Oncogene (England) 21 (3): 460–74. DOI:10.1038/sj.onc.1205100. ISSN 0950-9232. PMID 11821958. 
  10. ↑ Anhuf, D; Weissenbach M, Schmitz J, Sobota R, Hermanns H M, Radtke S, Linnemann S, Behrmann I, Heinrich P C, Schaper F (September 2000). „Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation”. J. Immunol. (UNITED STATES) 165 (5): 2535–43. ISSN 0022-1767. PMID 10946280. 
  11. ↑ 11,0 11,1 Kim, H; Baumann H (December 1997). „Transmembrane domain of gp130 contributes to intracellular signal transduction in hepatic cells”. J. Biol. Chem. (UNITED STATES) 272 (49): 30741–7. DOI:10.1074/jbc.272.49.30741. ISSN 0021-9258. PMID 9388212. 
  12. ↑ Timmermann, Andreas; Küster Andrea, Kurth Ingo, Heinrich Peter C, Müller-Newen Gerhard (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. (Germany) 269 (11): 2716–26. DOI:10.1046/j.1432-1033.2002.02941.x. ISSN 0014-2956. PMID 12047380. 
  13. ↑ Mosley, B; De Imus C, Friend D, Boiani N, Thoma B, Park L S, 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. (UNITED STATES) 271 (51): 32635–43. DOI:10.1074/jbc.271.51.32635. ISSN 0021-9258. PMID 8999038. 
  14. ↑ Lee, I S; 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. (NETHERLANDS) 401 (2-3): 133–7. DOI:10.1016/S0014-5793(96)01456-1. ISSN 0014-5793. PMID 9013873. 
  15. ↑ Haan, C; Is'harc H, Hermanns H M, Schmitz-Van De Leur H, Kerr I M, Heinrich P C, Grötzinger J, Behrmann I (October 2001). „Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction”. J. Biol. Chem. (United States) 276 (40): 37451–8. DOI:10.1074/jbc.M106135200. ISSN 0021-9258. PMID 11468294. 
  16. ↑ Haan, Claude; Heinrich Peter C, Behrmann Iris (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. (England) 361 (Pt 1): 105–11. DOI:10.1042/0264-6021:3610105. ISSN 0264-6021. PMC 1222284. PMID 11742534. 
  17. ↑ Giordano, V; De Falco G, Chiari R, Quinto I, Pelicci P G, Bartholomew L, Delmastro P, Gadina M, Scala G (May 1997). „Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase”. J. Immunol. (UNITED STATES) 158 (9): 4097–103. ISSN 0022-1767. PMID 9126968. 

Literatura

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  • Ip NY, Nye SH, Boulton TG, et al. (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): 1121–32. DOI:10.1016/0092-8674(92)90634-O. PMID 1617725. 
  • Hibi M, Murakami M, Saito M, et al. (1991). „Molecular cloning and expression of an IL-6 signal transducer, gp130.”. Cell 63 (6): 1149–57. DOI:10.1016/0092-8674(90)90411-7. PMID 2261637. 
  • Taga T, Hibi M, Hirata Y, et al. (1989). „Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130.”. Cell 58 (3): 573–81. DOI:10.1016/0092-8674(89)90438-8. PMID 2788034. 
  • Rodriguez C, Grosgeorge J, Nguyen VC, et al. (1995). „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. DOI:10.1159/000133993. PMID 7736792. 
  • Narazaki M, Yasukawa K, Saito T, et al. (1993). „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. PMID 8353278. 
  • Davis S, Aldrich TH, Stahl N, et al. (1993). „LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor.”. Science 260 (5115): 1805–8. DOI:10.1126/science.8390097. PMID 8390097. 
  • Murakami M, Hibi M, Nakagawa N, et al. (1993). „IL-6-induced homodimerization of gp130 and associated activation of a tyrosine kinase.”. Science 260 (5115): 1808–10. DOI:10.1126/science.8511589. PMID 8511589. 
  • Sharkey AM, Dellow K, Blayney M, et al. (1996). „Stage-specific expression of cytokine and receptor messenger ribonucleic acids in human preimplantation embryos.”. Biol. Reprod. 53 (4): 974–81. DOI:10.1095/biolreprod53.4.974. PMID 8547494. 
  • Mosley B, De Imus C, Friend D, et al. (1997). „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. 
  • Lee IS, Liu Y, Narazaki M, et al. (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. 
  • Auguste P, Guillet C, Fourcin M, et al. (1997). „Signaling of type II oncostatin M receptor.”. J. Biol. Chem. 272 (25): 15760–4. DOI:10.1074/jbc.272.25.15760. PMID 9188471. 
  • Schiemann WP, Bartoe JL, Nathanson NM (1997). „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. DOI:10.1074/jbc.272.26.16631. PMID 9195977. 
  • Diamant M, Rieneck K, Mechti N, et al. (1997). „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. DOI:10.1016/S0014-5793(97)00750-3. PMID 9256256. 
  • Koshelnick Y, Ehart M, Hufnagl P, et al. (1997). „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. DOI:10.1074/jbc.272.45.28563. PMID 9353320. 
  • Kim H, Baumann H (1998). „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. 
  • Bravo J, Staunton D, Heath JK, Jones EY (1998). „Crystal structure of a cytokine-binding region of gp130.”. EMBO J. 17 (6): 1665–74. DOI:10.1093/emboj/17.6.1665. PMC 1170514. PMID 9501088. 
  • Barton VA, Hudson KR, Heath JK (1999). „Identification of three distinct receptor binding sites of murine interleukin-11.”. J. Biol. Chem. 274 (9): 5755–61. DOI:10.1074/jbc.274.9.5755. PMID 10026196. 
  • Hirota H, Chen J, Betz UA, et al. (1999). „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. DOI:10.1016/S0092-8674(00)80729-1. PMID 10219240. 
  • Tacken I, Dahmen H, Boisteau O, et al. (1999). „Definition of receptor binding sites on human interleukin-11 by molecular modeling-guided mutagenesis.”. Eur. J. Biochem. 265 (2): 645–55. DOI:10.1046/j.1432-1327.1999.00755.x. PMID 10504396. 
  • Chung TD, Yu JJ, Kong TA, et al. (2000). „Interleukin-6 activates phosphatidylinositol-3 kinase, which inhibits apoptosis in human prostate cancer cell lines.”. Prostate 42 (1): 1–7. DOI:10.1002/(SICI)1097-0045(20000101)42:1<1::AID-PROS1>3.0.CO;2-Y. PMID 10579793. 

Spoljašnje veze

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