Document Detail

Differential roles of ERK and JNK in early and late stages of neuritogenesis: a study in a novel PC12 model system.
MedLine Citation:
PMID:  12950460     Owner:  NLM     Status:  MEDLINE    
The rat pheochromocytoma PC12 cell line has been an invaluable model system for studying neuritogenesis. Nerve growth factor (NGF) elicits multiple aspects of neurite outgrowth in PC12 cells. It is therefore difficult to dissect and assign an individual signaling pathway to each stage of neuritogenesis. We have recently reported the isolation of a variant PC12 cell line, PC12-N1 (N1), which spontaneously extends neuritic processes and exhibits an increased sensitivity to NGF. Here, we show that, under different culture conditions, the cells display three distinct phases of neuritogenesis consisting of neurite initiation, rapid neurite elongation, and a maturation process characterized by the thickening of neurites and increase in cell soma sizes. We demonstrate that signaling through ERK, but not p38 or JNK, is required for the spontaneous neurite initiation and extension. Treatment with low concentrations of NGF induces rapid neurite elongation without affecting neurite branching and cell soma sizes. Such a rapid neurite outgrowth can be blocked by the inhibition of ERK, but not JNK, activities. In the presence of higher concentrations of NGF, the N1 cells undergo further differentiation with many characteristics of mature neurons in culture, e.g. larger cell soma and numerous branches/connections. This process can be completely blocked by inhibiting ERK or JNK activities using specific inhibitors. These results suggest that ERK and JNK signals play different roles in neuritogenesis, and that JNK activity is essential in the late stages of neuritogenesis. Furthermore, our results demonstrate that signaling dosage is important in the activation of a specific pathway, leading to distinctive biological outcomes.
Jingnan Xiao; Yuechueng Liu
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurochemistry     Volume:  86     ISSN:  0022-3042     ISO Abbreviation:  J. Neurochem.     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-09-02     Completed Date:  2003-10-17     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1516-23     Citation Subset:  IM    
Department of Pathology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
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MeSH Terms
Cell Differentiation / physiology
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology
Epidermal Growth Factor / pharmacology
JNK Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinases / antagonists & inhibitors,  metabolism*
Models, Neurological
Neurites / drug effects,  enzymology,  physiology*
Neurons / drug effects,  metabolism,  physiology*
PC12 Cells
p38 Mitogen-Activated Protein Kinases
Grant Support
Reg. No./Substance:
0/Enzyme Inhibitors; 62229-50-9/Epidermal Growth Factor; EC Mitogen-Activated Protein Kinases; EC Protein Kinases; EC Mitogen-Activated Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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