Document Detail

Apoptotic cell death in TrkA-overexpressing cells: kinetic regulation of ERK phosphorylation and caspase-7 activation.
MedLine Citation:
PMID:  18511888     Owner:  NLM     Status:  MEDLINE    
The TrkA tyrosine kinase is activated by autophosphorylation in response to NGF, and plays an important role in cell survival, differentiation, and apoptosis. To investigate its role in cell fate determination, we produced stable TrkA-inducible SK-N-MC and U2OS cell lines using the Tet-On system. Interestingly, TrkA overexpression induced substantial cell death even in the absence of NGF, by stimulating ERK phosphorylation and caspase-7 activation leading to PARP cleavage. TrkA-mediated cell death was shown by the annexin-V binding assay to be, at least in part, apoptotic in both SK-N-MC and U2OS cells. Furthermore, the truncated form (p18) of Bax accumulated in the TrkA-induced cells, suggesting that TrkA induces mitochondria-mediated apoptosis. NGF treatment augmented the cell death induced by TrkA overexpression. This TrkA-induced cell death was blocked by the tyrosine kinase inhibitors, K-252a and GW441756. Moreover, TrkA overexpression inhibited long-term proliferation of both the neuronal SK-N-MC cells and the non-neuronal U2OS cells, suggesting a potential role of TrkA as a tumor suppressor.
Eun Joo Jung; Deok Ryong Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-05-20
Journal Detail:
Title:  Molecules and cells     Volume:  26     ISSN:  1016-8478     ISO Abbreviation:  Mol. Cells     Publication Date:  2008 Jul 
Date Detail:
Created Date:  2008-08-05     Completed Date:  2008-10-09     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9610936     Medline TA:  Mol Cells     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  12-7     Citation Subset:  IM    
Department of Biochemistry and RINS, MRCND and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 660-751, Korea.
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MeSH Terms
Blotting, Western
Bone Neoplasms / metabolism,  pathology*
Caspase 7 / metabolism*
Colony-Forming Units Assay
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases / metabolism*
Flow Cytometry
G1 Phase / drug effects
Nerve Growth Factor / pharmacology
Neuroblastoma / metabolism,  pathology*
Osteosarcoma / metabolism,  pathology*
Protein Processing, Post-Translational
Receptor, trkA / metabolism*
Tumor Cells, Cultured / drug effects
Reg. No./Substance:
9061-61-4/Nerve Growth Factor; EC, trkA; EC Signal-Regulated MAP Kinases; EC 3.4.22.-/Caspase 7

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

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