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Basic fibroblast growth factor activates serum response factor gene expression by multiple distinct signaling

J A Spencer1, M L Major, R P Misra

  • 1Department of Biochemistry, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.

Molecular and Cellular Biology
|May 18, 1999
PubMed

Insights

Serum response factor (SRF) gene regulation involves distinct pathways. Basic fibroblast growth factor (bFGF) upregulates the SRF promoter via CArG-independent and CArG-dependent mechanisms, impacting cell growth and development.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Gene Regulation

Background:

  • Serum response factor (SRF) is crucial for mammalian cell responses to extracellular signals.
  • SRF regulates early response genes involved in cell growth and differentiation.
  • Regulation of the SRF gene itself is less understood than its transcriptional activation mechanism.

Purpose of the Study:

  • To elucidate the regulatory mechanisms of the SRF gene promoter in response to basic fibroblast growth factor (bFGF).
  • To identify distinct pathways involved in SRF promoter upregulation by bFGF.
  • To explore the role of specific regulatory elements like CArG boxes and ETS binding sites.

Main Methods:

  • Analysis of SRF promoter activity in response to bFGF stimulation.
  • Identification of key regulatory elements (ETS, Sp/Egr-1, CArG boxes) involved in SRF gene upregulation.
  • Investigation of signaling pathways (Rho, Ras) mediating promoter activation.

Main Results:

  • bFGF upregulates the SRF promoter through at least two independent mechanisms.
  • A CArG box-independent mechanism involves an ETS binding site.
  • A novel CArG box-dependent mechanism requires both Sp factor and CArG motifs for maximal stimulation.
  • The CArG box-dependent component is targeted by Rho, while the Sp site-dependent component is targeted by Ras.

Conclusions:

  • SRF promoter regulation by bFGF is complex, involving distinct CArG-dependent and independent pathways.
  • Rho and Ras signaling pathways differentially regulate SRF gene expression.
  • Findings have implications for understanding SRF and bFGF roles in cardiogenesis during development.

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