CDC25(Mm)/Ras-GRF1 regulates both Ras and Rac signaling pathways

Metello Innocenti, Renata Zippel, Riccardo Brambilla, Emmapaola Sturani

Research output: Contribution to journalArticle

Abstract

The Ras-GRF1 exchange factor molecule contains in addition to the catalytic domain two pleckstrin homology (PH1 and PH2), one IQ and one Dbl homology (DH) domains. In this study we investigated the role of such additional domains. We found that a Ras-GRF1 mutant lacking PH1 and IQ domains is sufficient to activate c-fos promoter in response to lysophosphatidic acid (LPA). The same mutant did not increase external stimuli-regulated kinase (ERK) activity, suggesting an additional mechanism for the induction of gene transcription. Isolated DH-PH2 module activates c-Jun NH2-terminal kinase and the c-fos promoter in response to LPA, providing the basis for an ERK-independent mechanism. These results provide evidence that Ras-GRF1 acts as a bifunctional molecule on both ERK-dependent and independent pathways. Copyright (C) 1999 Federation of European Biochemical Societies.

Original languageEnglish
Pages (from-to)357-362
Number of pages6
JournalFEBS Letters
Volume460
Issue number2
DOIs
Publication statusPublished - Oct 29 1999

Fingerprint

ras-GRF1
Phosphotransferases
Molecules
JNK Mitogen-Activated Protein Kinases
Transcription
Catalytic Domain
Genes
lysophosphatidic acid

Keywords

  • c-Jun NH-terminal kinase
  • External stimuli-regulated kinase
  • Lysophosphatidic acid
  • Rac
  • Ras
  • Ras-GRF1

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Innocenti, M., Zippel, R., Brambilla, R., & Sturani, E. (1999). CDC25(Mm)/Ras-GRF1 regulates both Ras and Rac signaling pathways. FEBS Letters, 460(2), 357-362. https://doi.org/10.1016/S0014-5793(99)01374-5

CDC25(Mm)/Ras-GRF1 regulates both Ras and Rac signaling pathways. / Innocenti, Metello; Zippel, Renata; Brambilla, Riccardo; Sturani, Emmapaola.

In: FEBS Letters, Vol. 460, No. 2, 29.10.1999, p. 357-362.

Research output: Contribution to journalArticle

Innocenti, M, Zippel, R, Brambilla, R & Sturani, E 1999, 'CDC25(Mm)/Ras-GRF1 regulates both Ras and Rac signaling pathways', FEBS Letters, vol. 460, no. 2, pp. 357-362. https://doi.org/10.1016/S0014-5793(99)01374-5
Innocenti, Metello ; Zippel, Renata ; Brambilla, Riccardo ; Sturani, Emmapaola. / CDC25(Mm)/Ras-GRF1 regulates both Ras and Rac signaling pathways. In: FEBS Letters. 1999 ; Vol. 460, No. 2. pp. 357-362.
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