Document Detail


Growth arrest of PC12 cells by nerve growth factor is dependent on the phosphatidylinositol 3-kinase/Akt pathway via p75 neurotrophin receptor.
MedLine Citation:
PMID:  12671996     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We recently isolated mutant PC12 cell clones (PC84 cells) by transfection of PC12 cells with nerve growth factor (NGF) cDNA. These cells secreted active NGF and extended short processes, but proliferated faster than the parental PC12 cells. Because the expression level of p75, a low-affinity receptor for NGF, was significantly low, we suspected that NGF signaling via p75 was necessary for the growth arrest of the PC12 cells, and this was shown to be the case by repressing p75 function in PC12 cells. In this study, we examined the downstream signaling of p75, which would ultimately evoke the growth arrest. NGF is known to induce rapid phosphorylation of MAP kinase and Akt in PC12 cells, whereas in PC84 cells, MAP kinase was phosphorylated but the phosphorylation level of Akt was very low under the serum-free condition. This finding suggested that the low expression level of p75 in PC84 cells was the reason for the low Akt activation. Because Akt is known to be activated via phosphatidylinositol (PI) 3-kinase, we treated PC12 cells with a PI3-kinase inhibitor, Wortmannin, and found these cells did not cease proliferation in the presence of NGF. Furthermore, anti-p75 neutralizing antibody reduced NGF-induced phosphorylation of Akt in PC12 cells under the serum-free condition. Because we had already shown that PC12 cells treated with anti-p75 neutralizing antibody did not cease proliferation in the presence of NGF, these results suggest that NGF activates Akt via p75, which is necessary for the NGF-induced growth arrest of PC12 cells.
Authors:
Hisanori Ito; Hiroshi Nomoto; Shoei Furukawa
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of neuroscience research     Volume:  72     ISSN:  0360-4012     ISO Abbreviation:  J. Neurosci. Res.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-02     Completed Date:  2003-06-12     Revised Date:  2012-06-22    
Medline Journal Info:
Nlm Unique ID:  7600111     Medline TA:  J Neurosci Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  211-7     Citation Subset:  IM    
Copyright Information:
Copyright 2003 Wiley-Liss, Inc.
Affiliation:
Laboratory of Molecular Biology, Gifu Pharmaceutical University, Gifu, Japan.
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MeSH Terms
Descriptor/Qualifier:
Androstadienes / pharmacology
Animals
Cell Division
Enzyme Inhibitors / pharmacology
Intracellular Fluid / metabolism
Nerve Growth Factor / metabolism*
PC12 Cells / drug effects,  metabolism*
Phosphatidylinositol 3-Kinases / metabolism*
Phosphorylation
Protein-Serine-Threonine Kinases*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-akt
Rats
Receptor, Nerve Growth Factor
Receptor, trkA / metabolism
Receptors, Nerve Growth Factor / metabolism*
Signal Transduction / physiology
Tumor Cells, Cultured
Chemical
Reg. No./Substance:
0/Androstadienes; 0/Enzyme Inhibitors; 0/Proto-Oncogene Proteins; 0/Receptor, Nerve Growth Factor; 0/Receptors, Nerve Growth Factor; 19545-26-7/wortmannin; 9061-61-4/Nerve Growth Factor; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Receptor, trkA; EC 2.7.11.1/Akt1 protein, rat; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt

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