EEF2K
EEF2K| EEF2K | |||||||||||||||||||||||||
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| 식별자 | |||||||||||||||||||||||||
| 별칭 | EEF2K, HSU93850, eEF-2K, 진핵연장계수 2 kinase, CAMKIII, Calmodulin 의존성 단백질 kinase III. | ||||||||||||||||||||||||
| 외부 ID | OMIM: 606968 MGI: 1195261 HomoloGene: 7299 GeneCard: EEF2K | ||||||||||||||||||||||||
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| 직교체 | |||||||||||||||||||||||||
| 종 | 인간 | 마우스 | |||||||||||||||||||||||
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| 앙상블 | |||||||||||||||||||||||||
| 유니프로트 | |||||||||||||||||||||||||
| RefSeq(mRNA) | |||||||||||||||||||||||||
| RefSeq(단백질) | |||||||||||||||||||||||||
| 위치(UCSC) | Cr 16: 22.21 – 22.29Mb | Chr 7: 120.44 – 120.51Mb | |||||||||||||||||||||||
| PubMed 검색 | [3] | [4] | |||||||||||||||||||||||
| 위키다타 | |||||||||||||||||||||||||
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진핵연장인자-2키나아제(eEF-2 kinase, eEF-2 kinase, eEF-2K)는 차모듈린 의존 단백질키나아제III(CAMKIII)와 칼슘/칼모둘린 의존성 진핵연장인자 2키나아제로도 알려져 있으며,[5] 인간에서 EEF2K 유전자에 의해 암호화된 효소다.[6][7]
함수
eEF-2 키나아제는 여러 개의 상향 신호를 단백질 합성의 규제에 연결하는, 칼모듈린 매개 신호 경로에서 보존도가 높은 단백질 키나아제다.진핵연장 인자 2(EEF2)를 인지하여 EEF2 기능을 억제한다.[6][8]
활성화
eEF-2K의 활성도는 칼슘과 칼모듈린에 의존한다.eEF-2K의 활성화는 순차적 2단계 메커니즘에 의해 진행된다.첫째, 칼슘-칼모둘린은 높은 친화력으로 결합하여 키나제 영역을 활성화시켜 Tr-348의 급속한 자기인산화를 촉발한다.[9][10]두 번째 단계에서는 Tr-348의 자동인산화가 키나제 영역의 알로스테릭 인산염 바인딩 포켓에 인광-Thr-348의 결합에 의해 지지될 가능성이 있는 키나제의 순응적 변화를 이끈다.이는 기질인 신장계수 2에 대한 eEF-2K의 활성도를 증가시킨다.[10]
eEF-2K는 Ser-500의 자가인산화를 통해 칼슘 독립적인 활동을 얻을 수 있다.그러나, 칼모듈린은 효소의 활동이 지속되려면 효소에 계속 묶여 있어야 한다.[9]
임상적 유의성
이 키나아제의 활성도는 많은 암에서 증가하며 항암 치료의 타겟이 될 수 있다.[6][11]
또한 eEF-2K는 뉴런 단백질 합성에 대한 규제를 통해 케타민의 급속한 항우울제 효과를 발휘할 수 있을 것으로 제안된다.[12]
암
EEF-2K 표현은 종종 유방암과 췌장암을 포함한 암세포에서 조절되며 세포증식, 생존, 운동성/이동, 침공 및 종양성 증식을 촉진한다.[13][14]
참조
- ^ a b c ENSG00000284161 GRCh38: 앙상블 릴리스 89: ENSG00000103319, ENSG00000284161 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리스 89: ENSMUSG00000035064 - 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.
- ^ "EEF2K Gene (Protein Coding)". GeneCards. Weizmann Institute of Science. Retrieved 4 November 2015.
Aliases for EEF2K Gene
Eukaryotic Elongation Factor 2 Kinase
Calcium/Calmodulin-Dependent Eukaryotic Elongation Factor 2 Kinase
EEF-2 Kinase
EC 2.7.11.20
EEF-2K
Calcium/Calmodulin-Dependent Eukaryotic Elongation Factor-2 Kinase
Calmodulin-Dependent Protein Kinase III - ^ a b c "Entrez Gene: EEF2K eukaryotic elongation factor-2 kinase".
- ^ Ryazanov AG, Ward MD, Mendola CE, Pavur KS, Dorovkov MV, Wiedmann M, Erdjument-Bromage H, Tempst P, Parmer TG, Prostko CR, Germino FJ, Hait WN (May 1997). "Identification of a new class of protein kinases represented by eukaryotic elongation factor-2 kinase". Proceedings of the National Academy of Sciences of the United States of America. 94 (10): 4884–9. Bibcode:1997PNAS...94.4884R. doi:10.1073/pnas.94.10.4884. PMC 24600. PMID 9144159.
- ^ Ryazanov AG, Spirin AS (Oct 1990). "Phosphorylation of elongation factor 2: a key mechanism regulating gene expression in vertebrates". The New Biologist. 2 (10): 843–50. PMID 1964087.
- ^ a b Tavares CD, O'Brien JP, Abramczyk O, Devkota AK, Shores KS, Ferguson SB, Kaoud TS, Warthaka M, Marshall KD, Keller KM, Zhang Y, Brodbelt JS, Ozpolat B, Dalby KN (Mar 2012). "Calcium/calmodulin stimulates the autophosphorylation of elongation factor 2 kinase on Thr-348 and Ser-500 to regulate its activity and calcium dependence". Biochemistry. 51 (11): 2232–45. doi:10.1021/bi201788e. PMC 3401519. PMID 22329831.
- ^ a b Tavares CD, Ferguson SB, Giles DH, Wang Q, Wellmann RM, O'Brien JP, Warthaka M, Brodbelt JS, Ren P, Dalby KN (Aug 2014). "The molecular mechanism of eukaryotic elongation factor 2 kinase activation". The Journal of Biological Chemistry. 289 (34): 23901–16. doi:10.1074/jbc.m114.577148. PMC 4156036. PMID 25012662.
- ^ Leprivier G, Remke M, Rotblat B, Dubuc A, Mateo AR, Kool M, Agnihotri S, El-Naggar A, Yu B, Somasekharan SP, Faubert B, Bridon G, Tognon CE, Mathers J, Thomas R, Li A, Barokas A, Kwok B, Bowden M, Smith S, Wu X, Korshunov A, Hielscher T, Northcott PA, Galpin JD, Ahern CA, Wang Y, McCabe MG, Collins VP, Jones RG, Pollak M, Delattre O, Gleave ME, Jan E, Pfister SM, Proud CG, Derry WB, Taylor MD, Sorensen PH (May 2013). "The eEF2 kinase confers resistance to nutrient deprivation by blocking translation elongation". Cell. 153 (5): 1064–79. doi:10.1016/j.cell.2013.04.055. PMC 4395874. PMID 23706743.
- ^ Monteggia LM, Gideons E, Kavalali ET (Jun 2013). "The role of eukaryotic elongation factor 2 kinase in rapid antidepressant action of ketamine". Biological Psychiatry. 73 (12): 1199–203. doi:10.1016/j.biopsych.2012.09.006. PMC 3574622. PMID 23062356.
- ^ Tekedereli I, Alpay SN, Tavares CD, Cobanoglu ZE, Kaoud TS, Sahin I, Sood AK, Lopez-Berestein G, Dalby KN, Ozpolat B (Mar 20, 2012). "Targeted silencing of elongation factor 2 kinase suppresses growth and sensitizes tumors to doxorubicin in an orthotopic model of breast cancer". PLOS ONE. 7 (7): e41171. Bibcode:2012PLoSO...741171T. doi:10.1371/journal.pone.0041171. PMC 3401164. PMID 22911754.
- ^ Ashour AA, Abdel-Aziz AA, Mansour AM, Alpay SN, Huo L, Ozpolat B (Jan 22, 2014). "Targeting elongation factor-2 kinase (eEF-2K) induces apoptosis in human pancreatic cancer cells". Apoptosis. 19 (1): 241–58. doi:10.1007/s10495-013-0927-2. PMID 24193916. S2CID 16393302.
추가 읽기
- Nairn AC, Palfrey HC (Dec 1987). "Identification of the major Mr 100,000 substrate for calmodulin-dependent protein kinase III in mammalian cells as elongation factor-2". The Journal of Biological Chemistry. 262 (36): 17299–303. doi:10.1016/S0021-9258(18)45377-X. PMID 3693353.
- Redpath NT, Price NT, Severinov KV, Proud CG (Apr 1993). "Regulation of elongation factor-2 by multisite phosphorylation". European Journal of Biochemistry. 213 (2): 689–99. doi:10.1111/j.1432-1033.1993.tb17809.x. PMID 8386634.
- Pavur KS, Petrov AN, Ryazanov AG (Oct 2000). "Mapping the functional domains of elongation factor-2 kinase". Biochemistry. 39 (40): 12216–24. doi:10.1021/bi0007270. PMID 11015200.
- Diggle TA, Subkhankulova T, Lilley KS, Shikotra N, Willis AE, Redpath NT (Feb 2001). "Phosphorylation of elongation factor-2 kinase on serine 499 by cAMP-dependent protein kinase induces Ca2+/calmodulin-independent activity". The Biochemical Journal. 353 (Pt 3): 621–6. doi:10.1042/0264-6021:3530621. PMC 1221608. PMID 11171059.
- Knebel A, Morrice N, Cohen P (Aug 2001). "A novel method to identify protein kinase substrates: eEF2 kinase is phosphorylated and inhibited by SAPK4/p38delta". The EMBO Journal. 20 (16): 4360–9. doi:10.1093/emboj/20.16.4360. PMC 125581. PMID 11500363.
- Wang X, Li W, Williams M, Terada N, Alessi DR, Proud CG (Aug 2001). "Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase". The EMBO Journal. 20 (16): 4370–9. doi:10.1093/emboj/20.16.4370. PMC 125559. PMID 11500364.
- Arora S, Yang JM, Craft J, Hait W (May 2002). "Detection of anti-elongation factor 2 kinase (calmodulin-dependent protein kinase III) antibodies in patients with systemic lupus erythematosus". Biochemical and Biophysical Research Communications. 293 (3): 1073–6. doi:10.1016/S0006-291X(02)00324-8. PMID 12051769.
- Wistow G, Bernstein SL, Wyatt MK, Fariss RN, Behal A, Touchman JW, Bouffard G, Smith D, Peterson K (Jun 2002). "Expressed sequence tag analysis of human RPE/choroid for the NEIBank Project: over 6000 non-redundant transcripts, novel genes and splice variants". Molecular Vision. 8: 205–20. PMID 12107410.
- Knebel A, Haydon CE, Morrice N, Cohen P (Oct 2002). "Stress-induced regulation of eukaryotic elongation factor 2 kinase by SB 203580-sensitive and -insensitive pathways". The Biochemical Journal. 367 (Pt 2): 525–32. doi:10.1042/BJ20020916. PMC 1222910. PMID 12171600.
- Browne GJ, Finn SG, Proud CG (Mar 2004). "Stimulation of the AMP-activated protein kinase leads to activation of eukaryotic elongation factor 2 kinase and to its phosphorylation at a novel site, serine 398". The Journal of Biological Chemistry. 279 (13): 12220–31. doi:10.1074/jbc.M309773200. PMID 14709557.
- Browne GJ, Proud CG (Apr 2004). "A novel mTOR-regulated phosphorylation site in elongation factor 2 kinase modulates the activity of the kinase and its binding to calmodulin". Molecular and Cellular Biology. 24 (7): 2986–97. doi:10.1128/MCB.24.7.2986-2997.2004. PMC 371112. PMID 15024086.
- Brill LM, Salomon AR, Ficarro SB, Mukherji M, Stettler-Gill M, Peters EC (May 2004). "Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry". Analytical Chemistry. 76 (10): 2763–72. doi:10.1021/ac035352d. PMID 15144186.
- Li X, Alafuzoff I, Soininen H, Winblad B, Pei JJ (Aug 2005). "Levels of mTOR and its downstream targets 4E-BP1, eEF2, and eEF2 kinase in relationships with tau in Alzheimer's disease brain". The FEBS Journal. 272 (16): 4211–20. doi:10.1111/j.1742-4658.2005.04833.x. PMID 16098202. S2CID 43085490.
- Kimura K, Wakamatsu A, Suzuki Y, Ota T, Nishikawa T, Yamashita R, Yamamoto J, Sekine M, Tsuritani K, Wakaguri H, Ishii S, Sugiyama T, Saito K, Isono Y, Irie R, Kushida N, Yoneyama T, Otsuka R, Kanda K, Yokoi T, Kondo H, Wagatsuma M, Murakawa K, Ishida S, Ishibashi T, Takahashi-Fujii A, Tanase T, Nagai K, Kikuchi H, Nakai K, Isogai T, Sugano S (Jan 2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes". Genome Research. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
- Hait WN, Wu H, Jin S, Yang JM (2007). "Elongation factor-2 kinase: its role in protein synthesis and autophagy". Autophagy. 2 (4): 294–6. doi:10.4161/auto.2857. PMID 16921268.
- Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (Oct 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292.
- Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (Nov 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
