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Published online 3 June 2002. doi:10.1083/jcb.200109033
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© The Rockefeller University Press, 0021-9525/2002/6/929 $5.00
The Journal of Cell Biology, Volume 157, Number 6, June 10, 2002 929-940

Article

c-erbB-3

: a nuclear protein in mammary epithelial cells



Martin Offterdinger1, Christian Schöfer2, Klara Weipoltshammer2 and Thomas W. Grunt1

1 Signaling Networks Program, Division of Oncology, Department of Internal Medicine I, University of Vienna, A-1097 Vienna, Austria
2 Institute for Histology and Embryology, University of Vienna, A-1090 Vienna, Austria

Address correspondence to Thomas W. Grunt, Signaling Networks Program, Div. of Oncology, Dept. of Internal Medicine I, University of Vienna, Währinger Gürtel 18-20, A-1097 Vienna, Austria. Tel.: 43-1-40400-5487. Fax: 43-1-40400-5465. E-mail: thomas.grunt{at}akh-wien.ac.at

c-erbB receptors are usually located in cell membranes and are activated by extracellular binding of EGF-like growth factors. Unexpectedly, using immunofluorescence we found high levels of c-erbB-3 within the nuclei of MTSV1-7 immortalized nonmalignant human mammary epithelial cells. Nuclear localization was mediated by the COOH terminus of c-erbB-3, and a nuclear localization signal was identified by site-directed mutagenesis and by transfer of the signal to chicken pyruvate kinase. A nuclear export inhibitor caused accumulation of c-erbB-3 in the nuclei of other mammary epithelial cell lines as demonstrated by immunofluorescence and biochemical cell fractionation, suggesting that c-erbB-3 shuttles between nuclear and nonnuclear compartments in these cells. Growth of MTSV1-7 on permeable filters induced epithelial polarity and concentration of c-erbB-3 within the nucleoli. However, the c-erbB-3 ligand heregulin ß1 shifted c-erbB-3 from the nucleolus into the nucleoplasm and then into the cytoplasm. The subcellular localization of c-erbB-3 obviously depends on exogenous stimuli and on the stage of epithelial polarity and challenges the specific function of c-erbB-3 as a transmembrane receptor protein arguing for additional, as yet unidentified, roles of c-erbB-3 within the nucle(ol)us of mammary epithelial cells.

Key Words: c-erbB-3; epithelial polarity; heregulin; mammary epithelial cells; nuclear localization


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