Oncogenic and transcriptional cooperation with Ha-Ras requires phosphorylation of c-Jun on serines 63 and 73

Academic Article


  • RECENT advances indicate a link between tumour promoters, transformation, and AP-1 activity1. Protein kinase C activation increases AP-1 DNA-binding activity independently of new protein synthesis2,3. AP-1 is also stimulated by transforming oncoproteins and growth factors4-6. These proteins are thought to participate in a signalling cascade affecting the nuclear AP-1 complex composed of the Jun and Fos proteins1,7,8. Because c-Jun is the most potent transactivator in the AP-1 complex9-12 and is elevated in Ha-ras-transformed cells, in which c-Fos is downregulated13,14, we focused on it as a potential target. c-Jun could convert input from an oncogenic signalling cascade into changes in gene expression. Indeed, transformation of rat embryo fibroblasts by c-Jun requires an intact transcriptional activation domain15 and cooperation with oncogenic Ha-ras16. Expression of oncogenic Ha-ras augments transactivation by c-Jun and stimulates its phosphorylation14. Here we describe the mapping of the Ha-ras-responsive phosphorylation sites to serines 63 and 73 of c-Jun. Site-directed mutagenesis indicates that phosphorylation of these serines is essential for stimulation of c-Jun activity and for cooperation with Ha-ras in ocogenic transformation. © 1991 Nature Publishing Group.
  • Published In

  • Nature  Journal
  • Digital Object Identifier (doi)

    Author List

  • Smeal T; Binetruy B; Mercola DA; Birrer M; Karin M
  • Start Page

  • 494
  • End Page

  • 496
  • Volume

  • 354
  • Issue

  • 6353