NDLI: Involvement of cAMP in nerve growth factor-triggered p35/Cdk5 activation and differentiation in PC12 cells.

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Involvement of cAMP in nerve growth factor-triggered p35/Cdk5 activation and differentiation in PC12 cells.

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Involvement of cAMP in nerve growth factor-triggered p35/Cdk5 activation and differentiation in PC12 cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Chen, Mei-Chih Lin, Ho Hsu, Fu-Ning Huang, Pao-Hsuan Lee, Guan-Shun Wang, Paulus S.
Description	Country affiliation: China Author Affiliation: Chen MC ( Dept. of Physiology, School of Medicine, National Yang Ming University, Taipei 11221, Taiwan, Republic of China.)
Abstract	The signaling mechanisms underlying cell differentiation have been extensively studied with the use of rat PC12 cells as a model system. Nerve growth factor (NGF) is a trophic factor inducing PC12 cell differentiation through the activation of the p35/cyclin-dependent kinase 5 (Cdk5) complex. It has been reported that adenylyl cyclase activation and cAMP production may be involved in NGF-dependent actions. Our previous results indicate that cAMP activates the p35/Cdk5 complex in reproductive cells. Therefore, the role of cAMP in NGF-triggered p35/Cdk5 activation and PC12 differentiation was interesting to explore. Our results indicate that roscovitine, a molecular inhibitor of Cdk5, blocks cAMP-triggered PC12 differentiation, which was evaluated by neurite initiation, a decrease in proliferation, and cell cycle G(1) arrest. The following data show that cAMP treatment increased Cdk5 activity through p35 upregulation. cAMP downstream components, protein kinase A (PKA) and phosphorylated cAMP response element binding protein (CREB), are involved in this regulation. The immunocytochemical results indicate that PKA inhibition disrupted cAMP-triggered p35/Cdk5 localization in PC12 cells. In addition, adenylyl cyclase inhibition was found to diminish NGF-induced intracellular cAMP production, CREB phosphorylation, and p35 expression. The cAMP antagonist and the PKA inhibitors reduced NGF-induced p35 expression. Finally, NGF-triggered PC12 differentiation was partially decreased by adenylyl cyclase or PKA inhibitors. In conclusion, these results demonstrate that cAMP may play a role in NGF-p35/Cdk5-dependent PC12 differentiation.
File Format	HTM / HTML
ISSN	03636143
e-ISSN	15221563
Journal	American Journal of Physiology - Cell Physiology
Issue Number	2
Volume Number	299
Language	English
Publisher	American Physiological Society
Publisher Date	2010-08-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Cell Biology Cell Differentiation Physiology Cyclic Amp Pharmacology Cyclin-dependent Kinase 5 Metabolism Nerve Growth Factor Phosphotransferases Animals Drug Effects Cells, Cultured Antagonists & Inhibitors Enzyme Activation Neurites Enzymology Pc12 Cells Purines Comparative Study Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Cell Biology Physiology

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