Distinct responses of protein kinase C isozymes to c-erbB-2 activation in SKBR-3 human breast carcinoma cells

M. H. Disatnik, A. R. Winnier, D. Mochly-Rosen, C. L. Arteaga

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23 Scopus citations

Abstract

We have studied the effect of activation of the c-erbB-2 receptor tyrosine kinase on protein kinase C (PKC) in cultured SKBR-3 human breast cancer cells. Treatment with the agonistic anti-receptor monoclonal antibody TAb 250 induces receptor autophosphorylation and stimulates phospholipase C-γ1 (L. K. Shawver et al. Cancer Res., 54: 1367-1373, 1994). TAb 250 induced a rapid and marked translocation of PKC histone phosphorylation activity to the particulate fraction of SKBR-3 cells. By immunoblot, however, this translocation was limited to specific PKC isozymes. βPKC and ζPKC translocated to the particulate fraction, whereas εPKC underwent 'partial reversed translocation' to the cell soluble fraction after receptor stimulation. Furthermore, βPKC was rapidly degraded following TAb 250 treatment. By immunocytochemistry, βPKC translocated from the perinuclear area to the cytosol and into the nucleus, whereas ζPKC translocated to the perinuclear region and into the nucleus. Consistent with the Western blot results, εPKC translocated from the nucleus to the perinuclear area and the cytosol. These changes in the localization of PKC isozymes were not observed after addition of normal IgG1 or a nonagonistic anti-c-erbB-2 monoclonal antibody to SKBR-3 cells. α, βII, or δPKC present in these cells did not translocate following receptor stimulation. These data indicate that c-erbB- 2 signal transduction may involve the activation of specific PKC isozymes. The biological role of these enzymes in the phenotype and cellular responses of c-erbB-2-overexpressing carcinoma cells remains to be studied.

Original languageEnglish (US)
Pages (from-to)873-880
Number of pages8
JournalCell Growth and Differentiation
Volume5
Issue number8
StatePublished - Jan 1 1994

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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