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  • The EMBO Journal (1998) 17, 4046 - 4055
  • doi:10.1093/emboj/17.14.4046

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

Sonja Kampfer1, Karina Hellbert1, Andreas Villunger1, Wolfgang Doppler1, Gottfried Baier2, Hans H. Grunicke1 and Florian Überall1

  1. Institute of Medical Chemistry and Biochemistry and the Institute of Medical Biology, University of Innsbruck, A-6020, Innsbruck, Austria
  2. Human Genetics, University of Innsbruck, A-6020, Innsbruck, Austria

Correspondence to:

Florian Überall, E-mail: Florian.Ueberall@uibk.ac.at

Received 18 December 1997; Accepted 12 May 1998; Revised 12 May 1998

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.

  • Keywords:

    • antisense RNA expression,
    • c-fos,
    • Ha-Ras,
    • mitogenic signal transduction,
    • protein kinase C isoenzymes