맵캅K2
MAPKAPK2
MAP키나제 활성 단백질키나제2는 인간에서 MAPKAPK2 유전자에 의해 암호화된 효소다.[5][6][7]
함수
이 유전자는 Ser/Thr 단백질 키나아제 계열의 구성원을 인코딩한다.이 키나제는 p38 MAP 키나제에 의해 직접 인산화를 통해 조절된다.p38 MAP키나아제와 함께 이 키나아제는 스트레스와 염증 반응, 핵 수출, 유전자 발현 조절, 세포 증식 등 많은 세포 과정에 관여하는 것으로 알려져 있다.열충격 단백질 HSP27은 체내 주요 직접 기질로 나타났다.이 유전자에 대해 두 개의 서로 다른 ISO 양식을 인코딩하는 두 개의 대본 변형이 발견되었다.[8]
혈관 장벽
MK2 통로는 액틴과[9] 비멘틴 리모델링을 통해 폐 내피 장벽의 건전성을 유지하고 보수하는 데 핵심적인 역할을 하는 것으로 입증되었다.p38에 의한 인산화 MK2 활성화는 전 세계 주요 사망원인인 급성호흡기조난증후군(ARDS)을 비롯한 60여 가지 의학적 조건과 연관된 혈관장벽을[7] 회복하고 혈관 누출을 수리하는 것으로 나타났다.[10][11]
SASP 시작
MAPKAPK2는 mTOR(라파마이신의 기계적 표적)에 의한 노년기 관련 분비 표현형(SASP)의 시작을 매개한다.[12][13]인터루킨 1 알파(IL1A)는 노년기 세포 표면에서 발견되며, NF-164B와의 양성 피드백 루프에 의해 SASP 인자 생성에 기여한다.[14][15]IL1A에 대한 mRNA의 번역은 mTOR 활동에 크게 의존한다.[16] mTOR 활동은 MAPKAPK2에 의해 중재되는 IL1A의 수준을 증가시킨다.[14]
참고 항목
상호작용
MAPKAPK2는 다음과 상호 작용하는 것으로 나타났다.
참조
- ^ a b c GRCh38: 앙상블 릴리스 89: ENSG00000162889 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG000016528 - 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.
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- ^ Pham T, Rubenfeld GD (April 2017). "Fifty Years of Research in ARDS. The Epidemiology of Acute Respiratory Distress Syndrome. A 50th Birthday Review". American Journal of Respiratory and Critical Care Medicine. 195 (7): 860–870. doi:10.1164/rccm.201609-1773CP. PMID 28157386. S2CID 23293950.
- ^ Yessenkyzy A, Saliev T, Zhanaliyeva M, Masoud AR, Umbayev B, Sergazy S, et al. (May 2020). "Polyphenols as Caloric-Restriction Mimetics and Autophagy Inducers in Aging Research". Nutrients. 12 (5): 1344. doi:10.3390/nu12051344. PMC 7285205. PMID 32397145.
- ^ Papadopoli D, Boulay K, Kazak L, Pollak M, Mallette F, Topisirovic I, Hulea L (2019). "mTOR as a central regulator of lifespan and aging". F1000Research. 8: 998. doi:10.12688/f1000research.17196.1. PMC 6611156. PMID 31316753.
- ^ a b Laberge RM, Sun Y, Orjalo AV, Patil CK, Freund A, Zhou L, et al. (August 2015). "MTOR regulates the pro-tumorigenic senescence-associated secretory phenotype by promoting IL1A translation". Nature Cell Biology. 17 (8): 1049–61. doi:10.1038/ncb3195. PMC 4691706. PMID 26147250.
- ^ Wang R, Yu Z, Sunchu B, Shoaf J, Dang I, Zhao S, et al. (June 2017). "Rapamycin inhibits the secretory phenotype of senescent cells by a Nrf2-independent mechanism". Aging Cell. 16 (3): 564–574. doi:10.1111/acel.12587. PMC 5418203. PMID 28371119.
- ^ Wang R, Sunchu B, Perez VI (August 2017). "Rapamycin and the inhibition of the secretory phenotype". Experimental Gerontology. 94: 89–92. doi:10.1016/j.exger.2017.01.026. PMID 28167236. S2CID 4960885.
- ^ a b Rane MJ, Coxon PY, Powell DW, Webster R, Klein JB, Pierce W, et al. (February 2001). "p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils". The Journal of Biological Chemistry. 276 (5): 3517–23. doi:10.1074/jbc.M005953200. PMID 11042204.
- ^ Janknecht R (November 2001). "Cell type-specific inhibition of the ETS transcription factor ER81 by mitogen-activated protein kinase-activated protein kinase 2". The Journal of Biological Chemistry. 276 (45): 41856–61. doi:10.1074/jbc.M106630200. PMID 11551945.
- ^ a b Yannoni YM, Gaestel M, Lin LL (April 2004). "P66(ShcA) interacts with MAPKAP kinase 2 and regulates its activity". FEBS Letters. 564 (1–2): 205–11. doi:10.1016/S0014-5793(04)00351-5. PMID 15094067.
- ^ Dondelinger Y, Delanghe T, Rojas-Rivera D, Priem D, Delvaeye T, Bruggeman I, et al. (October 2017). "MK2 phosphorylation of RIPK1 regulates TNF-mediated cell death". Nature Cell Biology. 19 (10): 1237–1247. doi:10.1038/ncb3608. PMID 28920952. S2CID 25779284.
추가 읽기
- Kapopara PR, von Felden J, Soehnlein O, Wang Y, Napp LC, Sonnenschein K, et al. (December 2014). "Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling and promotes endothelial healing after arterial injury". Thrombosis and Haemostasis. 112 (6): 1264–76. doi:10.1160/TH14-02-0174. PMID 25120198.
- Ben-Levy R, Hooper S, Wilson R, Paterson HF, Marshall CJ (September 1998). "Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2". Current Biology. 8 (19): 1049–57. doi:10.1016/S0960-9822(98)70442-7. PMID 9768359. S2CID 15627349.
- Stokoe D, Engel K, Campbell DG, Cohen P, Gaestel M (November 1992). "Identification of MAPKAP kinase 2 as a major enzyme responsible for the phosphorylation of the small mammalian heat shock proteins". FEBS Letters. 313 (3): 307–13. doi:10.1016/0014-5793(92)81216-9. PMID 1332886.
- Vulliet PR, Woodgett JR, Cohen P (November 1984). "Phosphorylation of tyrosine hydroxylase by calmodulin-dependent multiprotein kinase". The Journal of Biological Chemistry. 259 (22): 13680–3. doi:10.1016/S0021-9258(18)89798-8. PMID 6150037.
- Engel K, Schultz H, Martin F, Kotlyarov A, Plath K, Hahn M, et al. (November 1995). "Constitutive activation of mitogen-activated protein kinase-activated protein kinase 2 by mutation of phosphorylation sites and an A-helix motif". The Journal of Biological Chemistry. 270 (45): 27213–21. doi:10.1074/jbc.270.45.27213. PMID 7592979.
- Lavoie JN, Lambert H, Hickey E, Weber LA, Landry J (January 1995). "Modulation of cellular thermoresistance and actin filament stability accompanies phosphorylation-induced changes in the oligomeric structure of heat shock protein 27". Molecular and Cellular Biology. 15 (1): 505–16. doi:10.1128/MCB.15.1.505. PMC 232001. PMID 7799959.
- Sutherland C, Alterio J, Campbell DG, Le Bourdellès B, Mallet J, Haavik J, Cohen P (October 1993). "Phosphorylation and activation of human tyrosine hydroxylase in vitro by mitogen-activated protein (MAP) kinase and MAP-kinase-activated kinases 1 and 2". European Journal of Biochemistry. 217 (2): 715–22. doi:10.1111/j.1432-1033.1993.tb18297.x. PMID 7901013.
- Knauf U, Jakob U, Engel K, Buchner J, Gaestel M (January 1994). "Stress- and mitogen-induced phosphorylation of the small heat shock protein Hsp25 by MAPKAP kinase 2 is not essential for chaperone properties and cellular thermoresistance". The EMBO Journal. 13 (1): 54–60. doi:10.1002/j.1460-2075.1994.tb06234.x. PMC 394778. PMID 7905823.
- Freshney NW, Rawlinson L, Guesdon F, Jones E, Cowley S, Hsuan J, Saklatvala J (September 1994). "Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27". Cell. 78 (6): 1039–49. doi:10.1016/0092-8674(94)90278-X. PMID 7923354. S2CID 37608621.
- Rivera VM, Miranti CK, Misra RP, Ginty DD, Chen RH, Blenis J, Greenberg ME (October 1993). "A growth factor-induced kinase phosphorylates the serum response factor at a site that regulates its DNA-binding activity". Molecular and Cellular Biology. 13 (10): 6260–73. doi:10.1128/mcb.13.10.6260. PMC 364685. PMID 8413226.
- Beyaert R, Cuenda A, Vanden Berghe W, Plaisance S, Lee JC, Haegeman G, et al. (April 1996). "The p38/RK mitogen-activated protein kinase pathway regulates interleukin-6 synthesis response to tumor necrosis factor". The EMBO Journal. 15 (8): 1914–23. doi:10.1002/j.1460-2075.1996.tb00542.x. PMC 450110. PMID 8617238.
- Ben-Levy R, Leighton IA, Doza YN, Attwood P, Morrice N, Marshall CJ, Cohen P (December 1995). "Identification of novel phosphorylation sites required for activation of MAPKAP kinase-2". The EMBO Journal. 14 (23): 5920–30. doi:10.1002/j.1460-2075.1995.tb00280.x. PMC 394711. PMID 8846784.
- Tan Y, Rouse J, Zhang A, Cariati S, Cohen P, Comb MJ (September 1996). "FGF and stress regulate CREB and ATF-1 via a pathway involving p38 MAP kinase and MAPKAP kinase-2". The EMBO Journal. 15 (17): 4629–42. doi:10.1002/j.1460-2075.1996.tb00840.x. PMC 452194. PMID 8887554.
- Huang CK, Zhan L, Ai Y, Jongstra J (January 1997). "LSP1 is the major substrate for mitogen-activated protein kinase-activated protein kinase 2 in human neutrophils". The Journal of Biological Chemistry. 272 (1): 17–9. doi:10.1074/jbc.272.1.17. PMID 8995217.
- Krump E, Sanghera JS, Pelech SL, Furuya W, Grinstein S (January 1997). "Chemotactic peptide N-formyl-met-leu-phe activation of p38 mitogen-activated protein kinase (MAPK) and MAPK-activated protein kinase-2 in human neutrophils". The Journal of Biological Chemistry. 272 (2): 937–44. doi:10.1074/jbc.272.2.937. PMID 8995385.
- Engel K, Kotlyarov A, Gaestel M (June 1998). "Leptomycin B-sensitive nuclear export of MAPKAP kinase 2 is regulated by phosphorylation". The EMBO Journal. 17 (12): 3363–71. doi:10.1093/emboj/17.12.3363. PMC 1170674. PMID 9628873.
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