Ras-dependent signal transduction is indispensable but not sufficient for the activation of AP1/Jun by PKCδ

Syu Ichi Hirai, Yasushi Izumi, Kenta Higa, Kozo Kaibuchi, Keiko Mizuno, Shin Ichi Osada, Koichi Suzuki, Shigeo Ohno

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113 Citations (Scopus)


Modulation of gene expression by 12-O-tetradecanoylphorbol-13-acetate (TPA) is thought to be mediated by protein kinase C (PKC), a major cellular receptor for TPA. We confirm this by showing that the overexpression of PKCδ enhances the TPA induction of the TRE-tk-CAT reporter gene in NIH3T3 cells. To investigate the mutual relationship between PKCδ- and Ras-dependent signal transduction pathways to a TRE binding transcription factor, AP1/Jun, we constructed constitutively active and dominant negative mutants of PKCδ. Activated Ras induced reporter gene expression in collaboration with overexpressed c-Jun or JunD, and this induction was insensitive to the dominant negative PKCδ. On the other hand, reporter gene expression induced by the constitutively active PKCδ was severely inhibited by dominant negative Ras, as well as by the dominant negative PKCδ. Thus, Ras activation must be indispensable for PKCδ to activate AP1/Jun. In the absence of overexpressed c-Jun or JunD, activated Ras was, however, clearly less effective than constitutively active PKCδ which showed full activation of reporter gene expression by itself. This suggests the presence of an additional, Ras-independent, signaling pathway downstream of PKCδ to activate AP1/Jun. In spite of the remarkable ability of constitutively active PKCδ to activate TRE-tk-CAT expression, this mutant suppressed cell growth.

Original languageEnglish
Pages (from-to)2331-2340
Number of pages10
JournalEMBO Journal
Issue number10
Publication statusPublished - 1994
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)


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