Extracellular signal-regulated kinase and the small GTP-binding protein p21Rac1 are involved in the regulation of gene transcription by angiotensin II

Tamás Huszár, István Mucsi, Balázs Antus, Tamás Terebessy, Csaba Jeney, András Masszi, László Hunyady, Balázs Mihalik, Howard J. Goldberg, Thomas J. Thekkumkara, László Rosivall

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6 Citations (Scopus)

Abstract

To study the role of extracellular-signal-regulated kinase (ERK) cascade and the small GTP-ase proteins in the activation of the c-fos promoter by angiotensin II (AII), transient transfection experiments were performed in CHO cells stably expressing the rat AT1A receptor. In this system AII activated ERK in 1 min and also increased the transcriptional activity of the c-fos promoter-luciferase reporter gene construct. The activation of the promoter proved to be dependent on the Ras-Raf-ERK cascade as cotransfection of expression vectors known to specifically inhibit this cascade blocked the effect of AII. Dominant-negative p21Rac1 mutant partially blocked the activation of the c-fos promoter by AII. However, activation of the c-fos promoter was independent of protein kinase C (PKC) as bisindolylmaleimide I, a specific PKC inhibitor did not block the effect of AII. These results suggest that AII activates the transcription of the c-fos through the Ras-Raf-ERK cascade. Furthermore, p21Rac1 is involved in the modulation of the c-fos promoter by AII.

Original languageEnglish
Pages (from-to)142-149
Number of pages8
JournalExperimental nephrology
Volume9
Issue number2
Publication statusPublished - Jan 17 2001

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Keywords

  • AT receptor
  • Angiotensin II
  • Mitogen-activated protein kinase pathway
  • Signal transduction
  • Transcription regulation

ASJC Scopus subject areas

  • Nephrology

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