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Plasminogen/plasmin regulates alpha-enolase expression through the MEK/ERK pathway
Lirlândia P Sousa1, Breno M Silva, Bruno S A F Brasil
1Grupo de Transdução de Sinal, Departamento de Microbiologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, Minas Gerais, Brazil.
Biochemical and Biophysical Research Communications
|October 18, 2005
Summary
Plasminogen (Plg) and plasmin (Pla) activate the MEK/ERK pathway, increasing alpha-enolase (alpha-ENO) gene expression in various cells. This process involves transcription factors and de novo protein synthesis.
Area of Science:
- Molecular Biology
- Cell Biology
- Biochemistry
Background:
- Plasminogen (Plg) and plasmin (Pla) are known regulators of transcription factors like c-FOS and EGR-1.
- The precise molecular mechanisms by which Plg and Pla influence gene expression require further elucidation.
Purpose of the Study:
- To investigate the role of Plg and Pla in regulating alpha-enolase (alpha-ENO) gene expression.
- To identify the signaling pathways involved in Plg/Pla-mediated alpha-ENO induction.
Main Methods:
- Treatment of fibroblasts and peripheral blood mononuclear cells with Plg and Pla.
- Analysis of alpha-ENO mRNA accumulation via quantitative methods.
- Pharmacological and genetic inhibition of the MEK/ERK pathway.
- Assessment of transcription factor DNA binding activity using electrophoretic mobility shift assays.
Main Results:
- Plg activates MEK and ERK, leading to increased alpha-ENO gene expression in both cell types.
- alpha-ENO mRNA levels were elevated for up to 28 hours post-Plg treatment.
- Plasmin's serine protease activity is essential for mimicking Plg-induced alpha-ENO expression.
- MEK/ERK pathway blockade inhibited alpha-ENO mRNA accumulation.
- Plg stimulated DNA binding of activator-protein 1 and early growth response gene-1 to the alpha-ENO promoter.
Conclusions:
- Plg/Pla signaling regulates alpha-enolase expression via the MEK/ERK pathway.
- This regulation involves transcription factors AP-1 and EGR-1.
- The findings highlight a novel mechanism of gene regulation by the Plg/Pla system.