Transcriptional activation of c-fos by oncogenic Ha-Ras in mouse mammary epithelial cells requires the combined activities of PKC-λ, ε and ζ
Open Access
- 15 July 1998
- journal article
- research article
- Published by Springer Nature in The EMBO Journal
- Vol. 17 (14) , 4046-4055
- https://doi.org/10.1093/emboj/17.14.4046
Abstract
The implication of protein kinase C (PKC) isoforms cPKC‐α, nPKC‐ϵ, aPKC‐λ and aPKC‐ζ 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‐λ, nPKC‐ϵ and aPKC‐ζ, not, however, of cPKC‐α, 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‐λ acts upstream whereas aPKC‐ζ functions downstream of nPKC‐ϵ.Keywords
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