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Ribosomal subunit kinase-2 is required for growth factor-stimulated transcription of the c-Fos gene

J C Bruning1, J A Gillette, Y Zhao

  • 1Klinik II und Poliklinik für Innere Medizin and Center of Molecular Medicine der Universität zu Köln, Joseph Stelzmann Strasse 9, 50931 Cologne, Germany.

Proceedings of the National Academy of Sciences of the United States of America
|March 16, 2000
PubMed

Insights

Ribosomal subunit kinase 2 (Rsk-2) is essential for growth factor-induced c-Fos gene expression. Rsk-2 deficiency impairs Elk-1 and SRF activation without affecting CREB or MAPK pathways.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Gene Regulation

Background:

  • Ribosomal subunit kinases (Rsk) regulate transcription via phosphorylation of transcription factors.
  • Rsk proteins, including Rsk-2, are involved in cellular responses to growth factors.

Purpose of the Study:

  • To investigate the role of Rsk-2 in transcription factor activation and gene expression.
  • To characterize Rsk-2-deficient cell lines and their response to growth factors.

Main Methods:

  • Generation and characterization of Rsk-2-deficient mouse embryonic fibroblast cell lines using homologous recombination.
  • Analysis of gene expression (c-Fos) and transcription factor activation (Elk-1, SRF, CREB) following stimulation with platelet-derived growth factor (PDGF) and insulin-like growth factor (IGF)-1.
  • Assessment of mitogen-activated protein kinase (MAPK) pathway activation.

Main Results:

  • Rsk-2 knockout (KO) cells showed no detectable Rsk-2 protein, with normal Rsk-1 expression.
  • KO cells exhibited significantly reduced PDGF- and IGF-1-stimulated c-Fos expression.
  • This reduction was linked to impaired transcriptional activation of Elk-1 and serum response factor (SRF).
  • Elk-1 phosphorylation and MAPK pathway activation remained normal in KO cells.
  • CREB phosphorylation and transcriptional activation were unaffected in Rsk-2 KO cells.

Conclusions:

  • Rsk-2 is crucial for growth factor-mediated induction of c-Fos transcription.
  • Rsk-2 mediates the transcriptional activation of Elk-1 and SRF in response to PDGF and IGF-1.
  • Rsk-2 is not required for CREB activation or MAPK pathway signaling under these conditions.

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