Colocalization of the p185(HER2) oncoprotein and integrin α6β4 in Calu-3 lung carcinoma cells

M. Campiglio, E. Tagliabue, U. Srinivas, R. Pellegrini, S. Martignone, S. Menard, M. I. Colnaghi, L. Lombardi, P. C. Marchisio

Research output: Contribution to journalArticlepeer-review

Abstract

Anti-p185(HER2) monoclonal antibodies often show intense reactivity with the basement membrane of tumor cells that overexpress the HER2/neu gene product (p185(HER2)). To evaluate a possible interaction between p185(HER2) and adhesion molecules or their receptors, the polarity of p185(HER2) was tested in lung carcinoma cell line Calu-3, which overexpresses this protein, in cultures grown as confluent monolayers or as aggregates. MAb immunostaining patterns indicated that p185(HER2) is concentrated on the baso-lateral membrane of cells and that it colocalizes with the integrin α6β4 at the cell-cell junctions where laminin is also found. The same membrane region showed intense reactivity with antiphosphotyrosine antibodies. Furthermore, integrin clustering induced by the specific antibody was accompanied by the clustering of p185(HER2), as indicated by immunoelectron microscopy, and by a subsequent increase in p185(HER2) tyrosine phosphorylation. Treatment with exogenous laminin also resulted in increased basal levels of p185(HER2) phosphorylation. These data suggest a physical interaction between the integrin and the oncoprotein that might be functionally relevant in directly controlling the tyrosine phosphorylation of the catalytic domain of p185(HER2).

Original languageEnglish
Pages (from-to)409-418
Number of pages10
JournalJournal of Cellular Biochemistry
Volume55
Issue number4
Publication statusPublished - 1994

Keywords

  • HER2/neu
  • integrins
  • laminin
  • oncoprotein
  • tyrosine phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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