• membrana plazme • integralno sa membranom plazme
Biološki proces
• imunski odgovor • transdukcija signala vezana za receptore na ćelijskoj površini • pozitivna regulacija ćelijske proliferacije • regulacija Notch signalinog puta
Ortolozi
Vrsta
Čovek
Miš
Entrez
3572
16195
Ensembl
ENSG00000134352
ENSMUSG00000021756
UniProt
P40189
Q3TDT5
RefSeq (mRNA)
NM_002184
NM_010560
RefSeq (protein)
NP_002175
NP_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]
Sadržaj
1Karakteristike
2Gubitak gp130
3Prenos signala
4Interakcije
5Reference
6Literatura
7Spoljašnje veze
Karakteristike
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
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.
↑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”. Cell63 (6): 1149–1157. DOI:10.1016/0092-8674(90)90411-7. PMID 2261637.
↑Bravo et al.; Staunton, D; Heath, JK; Jones, EY (1998). „Crystal structure of a cytokine-binding region of gp130”. EMBO J17 (6): 1665–1674. DOI:10.1093/emboj/17.6.1665. PMC 1170514. PMID 9501088.
↑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”. Science260 (5115): 1808–1810. DOI:10.1126/science.8511589. PMID 8511589.
↑Kishimoto T, Akira S, Narazaki M, Taga T (1995). „Interleukin-6 family of cytokines and gp130”. Blood86 (4): 1243–1254. PMID 7632928.
↑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 Sci93 (1): 407–411. DOI:10.1073/pnas.93.1.407. PMC 40247. PMID 8552649.
↑Kishimoto T, Taga T, Akira S (1994). „Cytokine signal transduction”. Cell76 (2): 253–262. DOI:10.1016/0092-8674(94)90333-6. PMID 8293462.
↑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.
↑ 8,08,1Lehmann, 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.
↑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.
↑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.
↑ 11,011,1Kim, 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.
↑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.
↑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.
↑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.
↑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.
↑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.
↑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
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.”. Cell69 (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.”. Cell63 (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.”. Cell58 (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.”. Blood82 (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.”. Science260 (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.”. Science260 (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.”. Cell97 (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.”. Prostate42 (1): 1–7. DOI:10.1002/(SICI)1097-0045(20000101)42:1<1::AID-PROS1>3.0.CO;2-Y. PMID 10579793.