Cited by 789Protein Kinase Regulation and GTPase SignalingProtein Tyrosine PhosphatasesMelanoma and MAPK Pathways

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

Smeal, Tod, Binetruy, Bernard, Mercola, Daniel A., Birrer, Michael, Karin, Michael·1991·Nature

Abstract

Recent advances indicate a link between tumour promoters, transformation, and AP-1 activity. Protein kinase C activation increases AP-1 DNA-binding activity independently of new protein synthesis. AP-1 is also stimulated by transforming oncoproteins and growth factors. These proteins are thought to participate in a signalling cascade affecting the nuclear AP-1 complex composed of the Jun and Fos proteins. Because c-Jun is the most potent transactivator in the AP-1 complex and is elevated in Ha-ras-transformed cells, in which c-Fos is downregulated, 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 domain and cooperation with oncogenic Ha-ras. Expression of oncogenic Ha-ras augments transactivation by c-Jun and stimulates its phosphorylation. 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.

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Crossref · 10.1038/354494a0

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  • The transcriptional activity of c-Jun is increased following phosphorylation on Ser-63 and -73 by JNK.

    “The transcriptional activity of c-Jun is increased following phosphorylation on Ser-63 and -73 by JNK (34,46).”
  • Usually, the transcriptional activity of c-Jun is increased following phosphorylation on Ser-63 and -73 by JNK.

    “Usually, the transcriptional activity of c-Jun is increased following phosphorylation on Ser-63 and -73 by JNK (34,46).”

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Authors
Smeal, T., Binetruy, B., Mercola, D. A., Birrer, M., & Karin, M.
Affiliations
  • University of California San Diego (US)
  • National Institutes of Health (US)
Venue
Nature
Published
1991-12
Volume
354
Issue
6353
Pages
494-496
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
OpenAlex
W2042260090
Cited by
789
References
23
Citations by year
2026: 4 · 2025: 5 · 2024: 7 · 2023: 3 · 2022: 4 · 2021: 11 · 2020: 11 · 2019: 12 · 2018: 9 · 2017: 7 · 2016: 10 · 2015: 8 · 2014: 12 · 2013: 21 · 2012: 12
FWCI
15.61
Type
journal article
Language
en
Open access
closed
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
Keywords
c-Jun, Ha-ras, AP-1 transcription factor, oncogenic transformation, transactivation domain, c-fos, protein kinase C, oncogene cooperation, rat embryo fibroblasts, tumor promoters
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Cell Transformation, Neoplastic, Molecular Sequence Data, Phosphorylation, Serine, Transcription, Genetic, Transcriptional Activation, Oncogene Protein p21(ras), Gene Expression Regulation, Neoplastic, Mutagenesis, Site-Directed, 3T3 Cells, Proto-Oncogene Proteins c-jun, Mice, Rats

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