Document Detail

Binding-induced activation of overexpressed p185HER2 is essential in triggering neuronal differentiation of PC12 cells.
MedLine Citation:
PMID:  9361187     Owner:  NLM     Status:  MEDLINE    
To determine whether p185HER2 overexpression per se triggers p185HER2 cellular signaling or whether an extracellular signal is required, we transfected PC12 cells with the human erbB-2 proto-oncogene, and established a cell line that overexpresses p185HER2. PC12-HER2 cells, maintained in suspension culture or plated on a collagen layer, showed the same morphology and growth rate as PC12 and PC12 mock-transfected control cells. When treated with monoclonal antibody (MAb) MGr6 or other anti-p185HER2 MAbs, PC12-HER2 cells specifically underwent neuronal differentiation comparable to that induced by nerve growth factor (NGF), and the differentiation-inducing effect of the MAb was dramatically enhanced by the addition of a second anti-mouse IgG. MAb-induced cell differentiation correlated with p185HER2 phosphorylation, recruitment of Shc and Grb-2 transducer molecules into complexes, and MAPK phosphorylation. These data indicate the requirement for a specific binding-induced activation of the overexpressed p185HER2 receptor in inducing PC12 cell differentiation. PC12-HER2 cells represent a suitable system for selection of p185HER2-activating ligands (peptides, phage-displayed peptides or proteins) or specific inhibitors of its tyrosine kinase activity.
R Orlandi; C Formantici; M I Colnaghi; S Ménard
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  67     ISSN:  0730-2312     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  1997 Dec 
Date Detail:
Created Date:  1997-12-10     Completed Date:  1997-12-10     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  316-26     Citation Subset:  IM    
Division of Experimental Oncology E, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
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MeSH Terms
Antibodies, Monoclonal
Calcium-Calmodulin-Dependent Protein Kinases / analysis
Cell Differentiation
Gene Expression
Mitogen-Activated Protein Kinase 1 / analysis
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinases*
Neurons / cytology*
PC12 Cells
Phosphotyrosine / analysis
Receptor, erbB-2 / biosynthesis,  genetics,  physiology*
Signal Transduction
Reg. No./Substance:
0/Antibodies, Monoclonal; 21820-51-9/Phosphotyrosine; EC, erbB-2; EC Protein Kinases; EC Protein Kinase 1; EC Protein Kinase 3; EC Protein Kinases

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