Tags

Type your tag names separated by a space and hit enter

Basic fibroblast growth factor promotes glial cell-derived neurotrophic factor gene expression mediated by activation of ERK5 in rat C6 glioma cells.
Cell Signal. 2011 Apr; 23(4):666-72.CS

Abstract

Extracellular signal-regulated kinases (ERKs) play important physiological roles including proliferation, differentiation and gene expression. ERK5 contains kinase domain that shares homology with ERK1/2 and the T-E-Y activation motif at amino-terminal half, whereas the extended carboxy-terminal half is unique. Because the physiological role of ERK5 in glial cells remains unclear, we examined the involvement of ERK5 in expression of neurotrophic factors and cytokines in rat C6 glioma cells, comparing it with ERK1/2. Basic fibroblast growth factor (bFGF) induced both ERK5 and ERK1/2 phosphorylation in a time- and concentration-dependent manner. Among the neurotrophic factors and cytokines, bFGF induced significant gene expression of glial cell-derived neurotrophic factor (GDNF). The GDNF gene expression and protein synthesis induced by bFGF were blocked by BIX02189 and PD98059 that selectively inhibit ERK5 and ERK1/2 signaling, respectively. The effect was also blocked by overexpression of a dominant-negative MEK5 mutant, indicating that GDNF expression induced by bFGF requires both ERK5 and ERK1/2. Because GDNF gene expression is regulated by various transcription factors, we examined the activity of these factors. We demonstrated that phosphorylation of cAMP-response element-binding protein at Ser 133 was induced by bFGF, which was blocked by BIX02189 and PD98059. Expression of c-fos, a major component of activator protein-1, and early growth response-1 was enhanced by bFGF, and expression of these genes was blocked by BIX02189, PD98059 and overexpression of dominant-negative MEK5. Taking these results together, bFGF promotes GDNF expression accompanied by the activation of ERK5, ERK1/2 and their downstream transcription factors in C6 glioma cells.

Authors+Show Affiliations

Department of Cellular Signaling, Graduate School of Pharmaceutical Sciences, Tohoku University, Aoba, Aramaki, Aoba-ku, Sendai, Japan. obaray@mail.pharm.tohoku.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21130871

Citation

Obara, Yutaro, et al. "Basic Fibroblast Growth Factor Promotes Glial Cell-derived Neurotrophic Factor Gene Expression Mediated By Activation of ERK5 in Rat C6 Glioma Cells." Cellular Signalling, vol. 23, no. 4, 2011, pp. 666-72.
Obara Y, Nemoto W, Kohno S, et al. Basic fibroblast growth factor promotes glial cell-derived neurotrophic factor gene expression mediated by activation of ERK5 in rat C6 glioma cells. Cell Signal. 2011;23(4):666-72.
Obara, Y., Nemoto, W., Kohno, S., Murata, T., Kaneda, N., & Nakahata, N. (2011). Basic fibroblast growth factor promotes glial cell-derived neurotrophic factor gene expression mediated by activation of ERK5 in rat C6 glioma cells. Cellular Signalling, 23(4), 666-72. https://doi.org/10.1016/j.cellsig.2010.11.020
Obara Y, et al. Basic Fibroblast Growth Factor Promotes Glial Cell-derived Neurotrophic Factor Gene Expression Mediated By Activation of ERK5 in Rat C6 Glioma Cells. Cell Signal. 2011;23(4):666-72. PubMed PMID: 21130871.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Basic fibroblast growth factor promotes glial cell-derived neurotrophic factor gene expression mediated by activation of ERK5 in rat C6 glioma cells. AU - Obara,Yutaro, AU - Nemoto,Wataru, AU - Kohno,Susumu, AU - Murata,Tomiyasu, AU - Kaneda,Norio, AU - Nakahata,Norimichi, Y1 - 2010/12/02/ PY - 2010/10/20/received PY - 2010/11/25/accepted PY - 2010/12/7/entrez PY - 2010/12/7/pubmed PY - 2011/5/7/medline SP - 666 EP - 72 JF - Cellular signalling JO - Cell Signal VL - 23 IS - 4 N2 - Extracellular signal-regulated kinases (ERKs) play important physiological roles including proliferation, differentiation and gene expression. ERK5 contains kinase domain that shares homology with ERK1/2 and the T-E-Y activation motif at amino-terminal half, whereas the extended carboxy-terminal half is unique. Because the physiological role of ERK5 in glial cells remains unclear, we examined the involvement of ERK5 in expression of neurotrophic factors and cytokines in rat C6 glioma cells, comparing it with ERK1/2. Basic fibroblast growth factor (bFGF) induced both ERK5 and ERK1/2 phosphorylation in a time- and concentration-dependent manner. Among the neurotrophic factors and cytokines, bFGF induced significant gene expression of glial cell-derived neurotrophic factor (GDNF). The GDNF gene expression and protein synthesis induced by bFGF were blocked by BIX02189 and PD98059 that selectively inhibit ERK5 and ERK1/2 signaling, respectively. The effect was also blocked by overexpression of a dominant-negative MEK5 mutant, indicating that GDNF expression induced by bFGF requires both ERK5 and ERK1/2. Because GDNF gene expression is regulated by various transcription factors, we examined the activity of these factors. We demonstrated that phosphorylation of cAMP-response element-binding protein at Ser 133 was induced by bFGF, which was blocked by BIX02189 and PD98059. Expression of c-fos, a major component of activator protein-1, and early growth response-1 was enhanced by bFGF, and expression of these genes was blocked by BIX02189, PD98059 and overexpression of dominant-negative MEK5. Taking these results together, bFGF promotes GDNF expression accompanied by the activation of ERK5, ERK1/2 and their downstream transcription factors in C6 glioma cells. SN - 1873-3913 UR - https://www.unboundmedicine.com/medline/citation/21130871/Basic_fibroblast_growth_factor_promotes_glial_cell_derived_neurotrophic_factor_gene_expression_mediated_by_activation_of_ERK5_in_rat_C6_glioma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0898-6568(10)00346-3 DB - PRIME DP - Unbound Medicine ER -