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Related Experiment Videos

v-Src activates mitogen-responsive transcription factor Egr-1 via serum response elements.

S A Qureshi1, X M Cao, V P Sukhatme

  • 1Institute for Biomolecular Structure and Function, Hunter College City University of New York, New York 10021.

The Journal of Biological Chemistry
|June 15, 1991
PubMed
Summary

Activating v-Src kinase increases Egr-1 gene expression via transcriptional control. This process relies on specific DNA elements called serum response elements (SREs) within the Egr-1 promoter.

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Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Genetics

Background:

  • v-Src is a protein-tyrosine kinase that regulates cell growth and proliferation.
  • Egr-1 is a transcription factor induced by mitogens, playing a role in cellular responses to growth factors.

Purpose of the Study:

  • To investigate the molecular mechanisms by which v-Src activates Egr-1 gene expression.
  • To identify the specific DNA sequences in the Egr-1 promoter responsible for v-Src-mediated transcriptional regulation.

Main Methods:

  • Deletion analysis of the Egr-1 promoter linked to a reporter gene.
  • Co-transfection of promoter constructs with a v-Src expression vector in NIH 3T3 fibroblasts.
  • Mutation analysis of specific DNA elements within the Egr-1 promoter.

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Main Results:

  • v-Src activation leads to increased Egr-1 expression, independent of protein synthesis and controlled at the transcriptional level.
  • v-Src-induced Egr-1 expression is dependent on CC(A/T)6GG elements, known as serum response elements (SREs).
  • The Egr-1 promoter contains four functional SREs that mediate v-Src responsiveness; deletion or mutation of these SREs abolishes the effect.

Conclusions:

  • v-Src signaling induces Egr-1 transcription through specific SREs in its promoter.
  • This transcriptional activation via SREs is an early event in v-Src-induced intracellular signaling pathways.
  • The findings elucidate a key mechanism linking oncogenic kinase activity to the regulation of immediate-early genes involved in cell growth.