Induction of cyclin-dependent kinase 5 and its activator p35 through the extracellular-signal-regulated kinase and protein kinase A pathways during retinoic-acid mediated neuronal differentiation in human neuroblastoma SK-N-BE(2)C cells
SCIE
SCOPUS
- Title
- Induction of cyclin-dependent kinase 5 and its activator p35 through the extracellular-signal-regulated kinase and protein kinase A pathways during retinoic-acid mediated neuronal differentiation in human neuroblastoma SK-N-BE(2)C cells
- Authors
- Lee, JH; Kim, KT
- Date Issued
- 2004-11
- Publisher
- BLACKWELL PUBLISHING LTD
- Abstract
- Cyclin-dependent kinase 5 (Cdk5), a neuronal Cdc2-like kinase, exhibits a variety of functions in neuronal differentiation and neurocytoskeleton dynamics, as well as neuronal degeneration. However, its role and induction mechanisms in retinoic acid (RA)-induced neuronal differentiation have not been well understood. In this study we newly found that RA treatment of SK-N-BE(2)C, human neuroblastoma cells, increased the expression of Cdk5 and its neuron specific activator p35 through the extracellular-signal-regulated kinase1/2 (ERK1/2) and cAMP-dependent protein kinase A (PKA) pathway. Inhibition of Cdk5 activity either by an inhibitor, roscovitine, or by transfection with a dominant negative form of Cdk5 caused a dramatic decrease in RA-induced differentiation, suggesting the requirement of Cdk5 kinase activity for the RA-induced neurite outgrowth. Furthermore, Cdk5 and p35 expression was decreased by ERK1/2 inhibition with PD98059 and increased by overexpression of a constitutive active mitogen-activated protein kinase kinase 1 (MEK1) mutant, suggesting the critical role of ERK1/2 in the induction of Cdk5 and p35. In addition, a transcription factor early growth response 1 (Egr-1) was induced by RA through the ERK1/2 pathway, suggesting its possible involvement in the p35 induction. RA treatment also induced c-fos mediated AP-1 binding, and cAMP-responsive element binding protein (CREB) mediated CRE binding via ERK1/2 and PKA pathway, respectively, in the Cdk5 promoter region, resulting in the induction of Cdk5. Our results suggest that ERK1/2 and PKA-induced regulation of Cdk5 activity possibly through Egr-1, c-fos, and CREB plays a critical role in the RA-induced neuronal differentiation.
- Keywords
- AP-1; extracellular-signal-regulated kinase; cyclin-dependent kinase 5; neuronal differentiation; p35; retinoic acid; EPIDERMAL-GROWTH-FACTOR; CENTRAL-NERVOUS-SYSTEM; PC12 CELLS; TYROSINE PHOSPHORYLATION; TRANSCRIPTION FACTORS; NEURITE OUTGROWTH; TERMINAL KINASE; IN-VIVO; CDK5; EXPRESSION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/17658
- DOI
- 10.1111/j.1471-4159.2004.02770.x
- ISSN
- 0022-3042
- Article Type
- Article
- Citation
- JOURNAL OF NEUROCHEMISTRY, vol. 91, no. 3, page. 634 - 647, 2004-11
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