ERK5信号通路研究现状
Review of the ERK5 Signaling Pathway Research

作者: 罗 松 , 苏胜发 , 欧阳伟炜 , 卢 冰 :贵阳医学院肿瘤学教研室,贵阳;

关键词: ERK5信号通路MAPKERK5 Signaling Pathways MAPK

摘要:
细胞外信号调节激酶5(extracellular signal regulated kinase, ERK5)是丝裂原活化蛋白激酶(mitogen activated protein kinase, MAPK)系统中的重要组成部分,也是MAPK信号转导通路中较新的一条通路,近几年备受人们关注。它可以被各种刺激因素激活,对细胞生存、增殖和分化有着重要作用,与血管发育、增殖等功能密切相关。本文从ERK5的来历、结构、性质、特点以及与肿瘤和非肿瘤疾病的关系,并对它以后的研究方向进行综述。

Abstract: Extracellular signal regulated kinase 5 (ERK5) is an important part of mitogen activated protein kinase (MAPK) system, and also is a new signal transduction pathway of MAPK signaling system, which has attracted much attention in recent years. ERK5 can be activated by many stimulating factors and plays an important role in cell survival, proliferation and differentiation. Furthermore, ERK5 is closely related to vascular development and proliferation, and other critical functions. This paper focuses on the origin, structure, property, physiological features of ERK5, and the relation-ship between ERK5 and tumor and non-oncologic diseases, and reviews the research direction in the future.

文章引用: 罗 松 , 苏胜发 , 欧阳伟炜 , 卢 冰 (2014) ERK5信号通路研究现状。 世界肿瘤研究, 4, 41-46. doi: 10.12677/WJCR.2014.44008

参考文献

[1] Roberts, O.L., Holmes, K., Muller, J., et al. (2009) ERK5 and the regulation of endothelial cell function. Biochemical Society Transactions, 37, 1254-1259.

[2] Hayashi, M., Kim, S.W., Imanaka-Yoshida, K., et al. (2004) Targeted dele-tion of BMK1/ERK5 in adult mice perturbs vascular integrity and leads to endothelial failure. Journal of Clinical In-vestigation, 113, 1138-1148.

[3] Wang, X. and Tournier, C. (2006) Regulation of cellular functions by the ERK5 signalling pathway. Cell Signal, 18, 753-760.

[4] Zhou, G., Bao, Z.Q. and Dixon, J.E. (1995) Components of a new human protein kinase signal transduction pathway. Journal of Biological Chemistry, 270, 12665-12669.

[5] Lee, J.D., Ulevitch, R.J. and Han, J. (1995) Primary structure of BMK1: A new mammalian map kinase. Biochemical and Bio-physical Research Communications, 213, 715-724.

[6] Spiering, D., Schmolke, M., Ohnesorge, N., et al. (2009) MEK5/ERK5 signaling modulates endothelial cell migration and focal contact turnover. Journal of Biological Chemistry, 284, 24972-24980.

[7] Carter, E.J., Cosgrove, R.A., Gonzalez, I., et al. (2009) MEK5 and ERK5 are mediators of the pro-myogenic actions of IGF-2. Journal of Cell Science, 122, 3104-3112.

[8] Yan, C., Luo, H., Lee, J.D., et al. (2001) Molecular cloning of mouse ERK5/BMK1 splice variants and characterization of ERK5 functional domains. Journal of Biological Chemistry, 276, 10870-10878.

[9] Morimoto, H., Kondoh, K., Nishimoto, S., et al. (2007) Activation of a C-terminal transcriptional activation domain of ERK5 by autophosphorylation. Journal of Biological Chemistry, 282, 35449-35456.

[10] Buschbeck, M. and Ullrich, A. (2005) The unique C-terminal tail of the mitogen-activated protein kinase ERK5 regulates its activation and nuclear shuttling. Journal of Biological Chemistry, 280, 2659-2667.

[11] Kamakura, S., Moriguchi, T. and Nishida, E. (1999) Activation of the protein kinase ERK5/BMK1 by receptor tyrosine kinases. Identification and characterization of a signaling pathway to the nucleus. Journal of Biological Chemistry, 274, 26563-26571.

[12] Nithianandarajah-Jones, G.N., Wilm, B., Goldring, C.E., Müller, J. and Cross, M.J. (2012) ERK5: Structure, regulation and function. Cellular Signalling, 24, 2187-2196.

[13] Kasler, H.G., Victoria, J., Duramad, O. and Winoto, A. (2000) ERK5 is a novel type of mitogen-activated protein kinase containing a transcriptional activation domain. Molecular and Cellular Biology, 20, 8382-8389.

[14] Sun, W., Kesavan, K., Schaefer, B.C., Garrington, T.P., Ware, M., Johnson, N.L., Gelfand, E.W. and Johnson, G.L. (2001) MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway. Journal of Biological Chemistry, 276, 5093-5100.

[15] Mody, N., Campbell, D.G., Morrice, N., Peggie, M. and Cohen, P. (2003) An analysis of the phosphorylation and activation of extracellular-signal-regulated protein kinase 5 (ERK5) by mitogen-activated protein kinase kinase 5 (MKK5) in vitro. Biochemical Journal, 372, 567-575.

[16] McCaw, B.J., Chow, S.Y., Wong, E.S., Tan, K.L., Guo, H. and Guy, G.R. (2005) Identification and characterization of mErk5-T, a novel Erk5/Bmk1 splice variant. Gene, 345, 183-190.

[17] English, J.M., Vanderbilt, C.A., Xu, S., Marcus, S. and Cobb, M.H. (1995) Isolation of MEK5 and differential expression of alternatively spliced forms. Journal of Biological Chemistry, 270, 28897-28902.

[18] Cude, K., Wang, Y., Choi, H.J., Hsuan, S.L., Zhang, H.L., Wang, C.Y. and Xia, Z.G. (2007) Reg-ulation of the G2-M cell cycle progression by the ERK5-NFkappaB signaling pathway. Journal of Cell Biology, 177, 253-264.

[19] Ye, M., Luo, X., Li, L., Shi, Y., Tan, M., Weng, X.X., Li, W., Liu, J.K. and Cao, Y. (2007) Grifolin, a potential antitumor natural product from the mushroom Albatrellus confluens, induces cell-cycle arrest in G1 phase via the ERK1/2 pathway. Cancer Letters, 258, 199-207.

[20] Lee, K.S., Park, J.H., Lim, H.J. and Park, H.Y. (2011) HB-EGF induces cardiomyocyte hypertrophy via an ERK5- MEF2A-COX2 signaling pathway. Cellular Signalling, 23, 1100-1109.

[21] Kato, Y., Tapping, R.I., Huang, S., Watson, M.H., Ulevitch, R.J. and Lee, J.D. (1998) Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature, 395, 713-716.

[22] Zhao, Z., Geng, J., Ge, Z.M., Wang, W., Zhang, Y. and Kang, W.Q. (2009) Activation of ERK5 in angiotensin II-induced hypertrophy of human aortic smooth muscle cells. Molecular and Cellular Biochemistry, 322, 171-178.

[23] Lochhead, P.A., Gilley, R. and Cook, S.J. (2012) ERK5 and its role in tumour development. Biochemical Society Transactions, 40, 251-256.

[24] Montero, J.C., Ocana, A., Abad, M., Ortiz-Ruiz, M.J., Pandiella, A. and Esparís-Ogando, A. (2009) Expression of Erk5 in early stage breast cancer and association with disease free survival identifies this kinase as a po-tential therapeutic target. PLoS ONE, 4, e5565.

[25] Antoon, J.W., Martin, E.C., Lai, R., Salvo, V.A., Tang, Y., Nitzchke, A.M., et al. (2013) MEK5/ERK5 signaling suppresses estrogen receptor expression and promotes hormone-independent tumorigenesis. PLoS ONE, 8, e69291.

[26] Zen, K., Yasui, K., Nakajima, T., Zen, Y., Zen, K., Gen, Y., et al. (2009) ERK5 is a target for gene amplification at 17p11 and promotes cell growth in hepatocellular carcinoma by regulating mitotic entry. Genes, Chromosomes and Cancer, 48, 109-120.

[27] Sticht, C., Freier, K., Knopfle, K., Flechtenmacher, C., Pungs, S., Hofele, C., Hahn, M., Joos, S. and Lichter, P. (2008) Activation of MAP kinase signaling through ERK5 but not ERK1 expression is associated with lymph node metastases in oral squamous cell carcinoma (OSCC). Neoplasia, 10, 462-470.

[28] McCracken, S.R., Ramsay, A., Heer, R., Mathers, M.E., Jenkins, B.L., Edwards, J., et al. (2008) Aberrant expression of extracellular signal-regulated kinase 5 in human prostate cancer. Oncogene, 27, 2978-2988.

[29] Ramsay, A.K., McCracken, S.R., Soofi, M., Fleming, J., Yu, A.X., Ahmad, I., et al. (2011) ERK5 signalling in prostate cancer promotes an invasive phenotype. British Journal of Cancer, 104, 664-672.

[30] Ramos-Nino, M.E., Blumen, S.R., Sabo-Attwood, T., Pass, H., Carbone, M., Testa, J.R., Altomare, D.A. and Mossman, B.T. (2008) HGF mediates cell proliferation of human mesothelioma cells through a PI3K/MEK5/Fra-1 pathway. American Journal of Respiratory Cell and Molecular Biology, 38, 209-217.

[31] Nagel, S., Burek, C., Venturini, L., Scherr, M., Quentmeier, H., Meyer, C., Rosenwald, A., Drexler, H.G. and MacLeod, R.A. (2007) Comprehensive analysis of homeobox genes in Hodgkin lymphoma cell lines identifies dysregulated expression of HOXB9 mediated via ERK5 signaling and BMI1. Blood, 109, 3015-3023.

[32] Lopez-Royuela, N., Rathore, M.G., Allende-Vega, N., Annicotte, J.S., Fajas, L., Ramachandran, B., Gulick, T. and Villalba, M. (2014) Extracellular-signal-regulated kinase 5 modulates the antioxidant response by transcriptionally controlling Sirtuin 1 expression in leukemic cells. International Journal of Biochemistry & Cell Biology, 53, 253-261.

[33] Castro, N.E. and Lange, C.A. (2010) Breast tumor kinase and extracellular signal-regulated kinase 5 mediate Met receptor signaling to cell migration in breast cancer cells. Breast Cancer Research, 12, R60.

[34] Hayashi, M., Fearns, C., Eliceiri, B., Yang, Y. and Lee, J.D. (2005) Big mitogen-activated protein kinase 1/extracellular signal-regulated kinase 5 signaling pathway is essential for tumor-associated angiogenesis. Cancer Research, 65, 7699- 7706.

[35] Kimura, T.E., Jin, J., Zi, M., Prehar, S., Liu, W., Oceandy, D., et al. (2010) Targeted deletion of the extracellular signal-regulated protein kinase 5 attenuates hypertrophic response and promotes pressure overload-induced apoptosis in the heart. Circulation Research, 106, 961-970.

[36] Le, N.T., Heo, K.S., Takei, Y., Lee, H., Woo, C.H., Chang, E., et al. (2013) A crucial role for p90RSK-mediated reduction of ERK5 transcriptional activity in endothelial dysfunction and atherosclerosis. Circulation, 127, 486-499.

[37] Wu, Y.X., Feng, B., Chen, S.L. and Chakrabarti, S. (2012) ERK5 Regulates glucose-induced increased fibronectin production in the endothelial cells and in the retina in diabetes. Investigative Ophthalmology & Visual Science, 53, 8405-8413.

[38] Fryer, R.M., Boustany-Kari, C.M. and MacDonnell, S.M. (2014) Engaging novel cell types, protein targets and efficacy biomarkers in the treatment of diabetic nephropathy. Frontiers in Pharmacology, 5, 185.

[39] Urushihara, M., Takamatsu, M., Shimizu, M., Kondo, S., Kinoshita, Y., Suga, K., et al. (2010) ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis. American Journal of Physiology-Renal Physiology, 298, 167-176.

[40] Katsarou, K., Tsitoura, P. and Georgopoulou, U. (2011) MEK5/ERK5/mef2: A novel signaling pathway affected by hepatitis C virus non-enveloped capsid-like particles. Biochimica et Biophysica Acta, 1813, 1854-1862.

[41] Li, P., Ma, Y.C., Shen, H.L., Han, H., Wang, J., Cheng, H.J., Wang, C.F. and Xia, Y.Y. (2012) Cytoskeletal reorganization mediates fluid shear stress-induced ERK5 activation in osteoblastic cells. Cell Biology International, 36, 229- 236.

[42] Gao, S.C., Yin, H.B., Liu, H.X. and Sui, Y.H. (2014) Research progress on MAPK signal pathway in the pathogenesis of osteoarthritis. Zhongguo Gu Shang, 27, 441-444.

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