Transcriptional activation of c-fos by oncogenic Ha-Ras in mouse mammary epithelial cells requires the combined activities of PKC-lambda, epsilon and zeta

EMBO J. 1998 Jul 15;17(14):4046-55. doi: 10.1093/emboj/17.14.4046.

Abstract

The implication of protein kinase C (PKC) isoforms cPKC-alpha, nPKC-epsilon, aPKC-lambda and aPKC-zeta in the transcriptional activation of a c-fos promoter-driven CAT-reporter construct by transforming Ha-Ras has been investigated. This was achieved by employing antisense constructs encoding RNA directed against isoform-specific 5' sequences of the corresponding mRNA, and expression of PKC mutants representing either kinase-defective, dominant negative, or constitutively active forms of the PKC isoforms. The data indicate that in HC11 mouse mammary epithelial cells, transforming Ha-Ras requires the activities of the three PKC isozymes: aPKC-lambda, nPKC-epsilon and aPKC-zeta, not, however, of cPKC-alpha, for the transcriptional activation of c-fos. Co-expression of oncogenic Ha-Ras with combinations of kinase-defective, dominant negative and constitutively active mutants of the various PKC isozymes are in agreement with a tentative model suggesting that, in the signaling pathway from Ha-Ras to the c-fos promoter, aPKC-lambda acts upstream whereas aPKC-zeta functions downstream of nPKC-epsilon.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Epithelial Cells / metabolism*
  • Genes, fos / genetics*
  • Isoenzymes / genetics
  • Isoenzymes / metabolism*
  • MAP Kinase Kinase 1
  • Mammary Glands, Animal / cytology
  • Mice
  • Mitogen-Activated Protein Kinase Kinases*
  • Oncogene Protein p21(ras) / metabolism*
  • Promoter Regions, Genetic / genetics
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism*
  • Protein-Serine-Threonine Kinases / physiology
  • Protein-Tyrosine Kinases / physiology
  • Proto-Oncogene Proteins c-raf / physiology
  • RNA, Antisense
  • Signal Transduction / genetics
  • Transcriptional Activation / physiology*
  • Transfection

Substances

  • Isoenzymes
  • RNA, Antisense
  • Protein-Tyrosine Kinases
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-raf
  • Protein Kinase C
  • MAP Kinase Kinase 1
  • Map2k1 protein, mouse
  • Mitogen-Activated Protein Kinase Kinases
  • Oncogene Protein p21(ras)