Oncogenic Ras activates c-Jun via a separate pathway from the activation of extracellular signal-regulated kinases

John K. Westwick, Adrienne D. Cox, Channing J. Der, Melanie H. Cobb, Masahiko Hibi, Michael Karin, David A. Brenner

Research output: Contribution to journalArticle

159 Citations (Scopus)

Abstract

c-Jun transcriptional activity is augmented by expression of oncogenic Ras and Raf proteins. This study demonstrates a direct correlation between Ras transforming activity and c-Jun activation, supporting an important role for c-Jun in transformation by Ras. Since we observed that Ras activated c-Jun transcriptional activity by increasing phosphorylation of the c-Jun activation domain at residues Ser-63/Ser-73 and that oncogenic Ras proteins activated extracellular signal-regulated protein kinases (ERK1 and ERK2) (also known as mitogen-activated protein kinases), we evaluated the possibility that ERKs were directly responsible for c-Jun activation. Coexpression of wild-type ERKs with oncogenic Ras proteins potentiated, while kinase-defective ERKs inhibited, Ras-induced transcriptional activation from the Ras-responsive element (Ets-1/AP-1) present in the NVL-3 enhancer and the serum-response element in the c-fos promoter. In contrast, coexpression of either wild-type or kinase-defective ERKs inhibited Ras and Raf activation of c-Jun transcriptional activity. Thus, although activation of both ERK and c- Jun are downstream consequences of activation of the Ras signal transduction pathway, our results suggest that Ras-induced c-Jun phosphorylation and transcriptional activation are not a direct consequence of ERK1 and ERK2 activation.

Original languageEnglish (US)
Pages (from-to)6030-6034
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number13
DOIs
StatePublished - Jun 21 1994

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ras Proteins
Extracellular Signal-Regulated MAP Kinases
Transcriptional Activation
Phosphotransferases
Serum Response Element
Phosphorylation
Transcription Factor AP-1
Mitogen-Activated Protein Kinases
Protein Kinases
Signal Transduction

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Oncogenic Ras activates c-Jun via a separate pathway from the activation of extracellular signal-regulated kinases. / Westwick, John K.; Cox, Adrienne D.; Der, Channing J.; Cobb, Melanie H.; Hibi, Masahiko; Karin, Michael; Brenner, David A.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 91, No. 13, 21.06.1994, p. 6030-6034.

Research output: Contribution to journalArticle

Westwick, John K. ; Cox, Adrienne D. ; Der, Channing J. ; Cobb, Melanie H. ; Hibi, Masahiko ; Karin, Michael ; Brenner, David A. / Oncogenic Ras activates c-Jun via a separate pathway from the activation of extracellular signal-regulated kinases. In: Proceedings of the National Academy of Sciences of the United States of America. 1994 ; Vol. 91, No. 13. pp. 6030-6034.
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