글리코프로틴 130
Glycoprotein 130
글리코프로틴 130(gp130, IL6ST, IL6R-베타 또는 CD130으로도 알려져 있음)은 모든 사이토카인 수용체 등급의 창립 멤버인 트랜섬브레인 단백질이다.IL-6 수용체군 내에서 I-사이토카인 수용체 1개 서브단위를 형성한다.흔히 공통 gp130 서브 유닛으로 불리며, 사이토카인 결합 후 신호 전달에 중요하다.다른 타입 I 사이토카인 수용체와 마찬가지로 gp130은 WSXWS 아미노산 모티브를 가지고 있어 정확한 단백질 접힘과 리간드 결합이 보장된다.그것은 야누스 키나제스와 상호작용하여 그것의 리간드와 수용체 상호작용에 따른 세포내 신호를 유도한다.구조적으로 gp130은 세포외부에 5개의 섬유질 III 도메인과 1개의 면역글로불린 유사 C2형(면역글로불린 유사) 도메인으로 구성되어 있다.[5][6]
특성.
IL-6 수용체 제품군의 구성원들은 모두 신호 전달을 위한 gp130으로 복잡하다.예를 들어, IL-6은 IL-6 수용체에 바인딩된다.이 두 단백질의 복합체는 gp130과 연관된다.3개의 단백질로 이루어진 이 복합체는 하류 신호를 생산할 수 있는 육각 복합체를 형성하기 위해 균질화된다.[7]gp130과 연관된 많은 다른 단백질들이 있는데, 카디오트로핀 1 (CT-1), 백혈병 억제 인자 (LIF), 담도 신경 위축 인자 (CNTF), oncostatin M (OSM), IL-11 등이 있다.[8]또한 gp130과 구조적 유사성을 가지고 있으며 WSXWS 모티브와 보존된 시스테인 잔류물을 함유하고 있는 몇 가지 다른 단백질도 있다.이 그룹의 멤버는 LIF-R, OSM-R 및 G-CSF-R을 포함한다.
gp130 손실
gp130은 많은 다른 유형의 신호 복합체에서 중요한 부분이다.gp130의 불활성화는 쥐에게 치명적이다.[9]태어난 균질 생쥐는 심실 심근의 발달장애를 포함한 많은 결함을 보여준다.조혈 효과는 비장과 간에서 줄기 세포의 수를 줄였다.
신호전달
gp130에는 고유의 tyrosine kinase 활동이 없다.대신 다른 단백질과 복합한 후 티로신 잔류물에 인산염화된다.인산화 작용은 JAC/Tyk tyrosine kinases 및 STAT 단백질 전사 인자와 연관된다.[10]특히 STAT-3가 활성화되어 많은 다운스트림 유전자가 활성화된다.활성화된 다른 경로로는 RAS 및 MAPK 신호가 있다.
상호작용
당단백질 130은 다음과 상호작용하는 것으로 나타났다.
- Grb2,[11]
- HER2/neu,[12]
- 야누스키나제1길[13][14][15]
- 백혈병 억제 인자 수용체,[16][17]
- PTPN11,[13][18][19]
- SHC1,[20]
- SOCS3 [18]및
- TLE1.[21]
참조
- ^ a b c GRCh38: 앙상블 릴리스 89: ENSG00000134352 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000021756 - 앙상블, 2017년 5월
- ^ "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 (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. S2CID 30852638.
- ^ Bravo J, 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.
- ^ 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. Bibcode:1993Sci...260.1808M. doi:10.1126/science.8511589. PMID 8511589.
- ^ Kishimoto T, Akira S, Narazaki M, Taga T (1995). "Interleukin-6 family of cytokines and gp130". Blood. 86 (4): 1243–1254. doi:10.1182/blood.V86.4.1243.bloodjournal8641243. 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 WZ, 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. Bibcode:1996PNAS...93..407Y. doi:10.1073/pnas.93.1.407. PMC 40247. PMID 8552649.
- ^ 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. S2CID 31924790.
- ^ Lee IS, 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. 401 (2–3): 133–7. doi:10.1016/s0014-5793(96)01456-1. PMID 9013873. S2CID 32632406.
- ^ Grant SL, Hammacher A, Douglas AM, Goss GA, Mansfield RK, Heath JK, Begley CG (January 2002). "An unexpected biochemical and functional interaction between gp130 and the EGF receptor family in breast cancer cells". Oncogene. 21 (3): 460–74. doi:10.1038/sj.onc.1205100. PMID 11821958.
- ^ a b Kim H, Baumann H (December 1997). "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.
- ^ Haan C, Is'harc H, Hermanns HM, Schmitz-Van De Leur H, Kerr IM, Heinrich PC, Grötzinger J, Behrmann I (October 2001). "Mapping of a region within the N terminus of Jak1 involved in cytokine receptor interaction". J. Biol. Chem. 276 (40): 37451–8. doi:10.1074/jbc.M106135200. PMID 11468294.
- ^ Haan C, Heinrich PC, Behrmann I (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): 105–11. doi:10.1042/0264-6021:3610105. PMC 1222284. PMID 11742534.
- ^ 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". Eur. J. Biochem. 269 (11): 2716–26. doi:10.1046/j.1432-1033.2002.02941.x. PMID 12047380.
- ^ Mosley B, De Imus C, Friend D, Boiani N, Thoma B, Park LS, 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. 271 (51): 32635–43. doi:10.1074/jbc.271.51.32635. PMID 8999038.
- ^ a b Lehmann U, Schmitz J, Weissenbach M, Sobota RM, Hortner M, Friederichs K, Behrmann I, Tsiaris W, Sasaki A, Schneider-Mergener J, Yoshimura A, Neel BG, Heinrich PC, Schaper F (January 2003). "SHP2 and SOCS3 contribute to Tyr-759-dependent attenuation of interleukin-6 signaling through gp130". J. Biol. Chem. 278 (1): 661–71. doi:10.1074/jbc.M210552200. PMID 12403768.
- ^ Anhuf D, Weissenbach M, Schmitz J, Sobota R, Hermanns HM, Radtke S, Linnemann S, Behrmann I, Heinrich PC, Schaper F (September 2000). "Signal transduction of IL-6, leukemia-inhibitory factor, and oncostatin M: structural receptor requirements for signal attenuation". J. Immunol. 165 (5): 2535–43. doi:10.4049/jimmunol.165.5.2535. PMID 10946280.
- ^ Giordano V, De Falco G, Chiari R, Quinto I, Pelicci PG, Bartholomew L, Delmastro P, Gadina M, Scala G (May 1997). "Shc mediates IL-6 signaling by interacting with gp130 and Jak2 kinase". J. Immunol. 158 (9): 4097–103. PMID 9126968.
- ^ Liu F, Liu Y, Li D, Zhu Y, Ouyang W, Xie X, Jin B (March 2002). "The transcription co-repressor TLE1 interacted with the intracellular region of gpl30 through its Q domain". Mol. Cell. Biochem. 232 (1–2): 163–7. doi:10.1023/A:1014880813692. PMID 12030375. S2CID 8270300.
추가 읽기
- Ip NY, Nye SH, Boulton TG, Davis S, Taga T, Li Y, Birren SJ, Yasukawa K, Kishimoto T, Anderson DJ (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. S2CID 45816061.
- Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T (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. S2CID 30852638.
- Taga T, Hibi M, Hirata Y, Yamasaki K, Yasukawa K, Matsuda T, Hirano T, Kishimoto T (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. S2CID 41245022.
- 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". Cytogenet. Cell Genet. 70 (1–2): 64–7. doi:10.1159/000133993. PMID 7736792.
- Narazaki M, Yasukawa K, Saito T, Ohsugi Y, Fukui H, Koishihara Y, Yancopoulos GD, Taga T, Kishimoto T (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. doi:10.1182/blood.V82.4.1120.1120. PMID 8353278.
- Davis S, Aldrich TH, Stahl N, Pan L, Taga T, Kishimoto T, Ip NY, Yancopoulos GD (1993). "LIFR beta and gp130 as heterodimerizing signal transducers of the tripartite CNTF receptor". Science. 260 (5115): 1805–8. Bibcode:1993Sci...260.1805D. doi:10.1126/science.8390097. PMID 8390097.
- 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): 1808–10. Bibcode:1993Sci...260.1808M. doi:10.1126/science.8511589. PMID 8511589.
- Sharkey AM, Dellow K, Blayney M, Macnamee M, Charnock-Jones S, Smith SK (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, Boiani N, Thoma B, Park LS, Cosman D (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, Hibi M, Kishimoto T, Taga T (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. S2CID 32632406.
- Auguste P, Guillet C, Fourcin M, Olivier C, Veziers J, Pouplard-Barthelaix A, Gascan H (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, Zhang XG, Svenson M, Bendtzen K, Klein B (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. S2CID 12420499.
- Koshelnick Y, Ehart M, Hufnagl P, Heinrich PC, Binder BR (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, Rajewsky K, Gu Y, Ross J, Müller W, Chien KR (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. S2CID 17955799.
- Tacken I, Dahmen H, Boisteau O, Minvielle S, Jacques Y, Grötzinger J, Küster A, Horsten U, Blanc C, Montero-Julian FA, Heinrich PC, Müller-Newen G (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, Spiotto MT, Lin JM (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.
외부 링크
- 미국 국립 의학 도서관의 Cytokine+Receptor+gp130(MesH)
PDB 갤러리 | |
|---|---|
|
