Binding-induced activation of overexpressed p185(HER2) is essential in triggering neuronal differentiation of PC12 cells

Rosaria Orlandi, Cristina Formantici, Maria I. Colnaghi, Sylvie Ménard

Research output: Contribution to journalArticle

Abstract

To determine whether p185 overexpression per se triggers p185(HER2) 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, p185(HER2). PC12-HER2 cells, maintained in suspension culture or plated on 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-p185(HER2) 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 p185(HER2) 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 p185(HER2) receptor in inducing PC12 cell differentiation. PC12-HER2 cells represent a suitable system for selection of p185(HER2)-activating ligands (peptides, phage-displayed peptides or proteins) or specific inhibitors of its tyrosine kinase activity.

Original languageEnglish
Pages (from-to)316-326
Number of pages11
JournalJournal of Cellular Biochemistry
Volume67
Issue number3
DOIs
Publication statusPublished - Dec 1 1997

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Keywords

  • Cell differentiation
  • ErbB-2/neu
  • Monoclonal antibodies
  • P185(HER2) overexpression
  • PC12

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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