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Published on: July 24, 2011
Enhancement of polyoma virus middle T antigen tyrosine phosphorylation by epidermal growth factor
Abstract:
Polyoma virus codes for three proteins involved in host cell transformation: the large, middle and small T antigens. Middle T antigen is a major transforming protein which is responsible for the induction of the phenotype of transformed cells and, without it, transformation does not occur (reviewed in refs 1-4). Middle T antigen alone can transform established cell lines, although large, and possibly small, T antigens are also required for the full expression of the phenotype of transformed cells in media with a low concentration of serum. A subfraction of middle T antigen is associated with a protein kinase activity which phosphorylates middle T antigen in vitro on tyrosine. There is a strong correlation between the level of this kinase activity and the degree of expression of the phenotype of transformed cells. We report here that epidermal growth factor (EGF) stimulates tyrosine phosphorylation of middle T antigen, suggesting the possibility that mitogenic growth factor(s) regulates this phosphorylation activity.
Insights
Polyoma virus middle T antigen drives cell transformation and is phosphorylated on tyrosine. Epidermal growth factor (EGF) stimulates this phosphorylation, suggesting growth factors regulate this key transformation activity.
Area of Science:
- Virology
- Molecular Biology
- Cellular Transformation
Background:
- Polyoma virus encodes large, middle, and small T antigens, crucial for host cell transformation.
- Middle T antigen is a primary transforming protein, essential for inducing the transformed cell phenotype.
- While middle T antigen alone can transform cells, other T antigens contribute to full transformation, especially in low serum conditions.
Purpose of the Study:
- To investigate the regulation of middle T antigen's protein kinase activity.
- To explore the role of growth factors in the phosphorylation of middle T antigen.
Main Methods:
- Biochemical assays to detect protein kinase activity associated with middle T antigen.
- In vitro phosphorylation studies using middle T antigen.
- Treatment with epidermal growth factor (EGF) to assess its effect on phosphorylation.
Main Results:
- A subfraction of middle T antigen exhibits associated protein kinase activity.
- This kinase activity phosphorylates middle T antigen on tyrosine residues in vitro.
- A strong correlation exists between kinase activity levels and the transformed cell phenotype.
- Epidermal growth factor (EGF) was found to stimulate the tyrosine phosphorylation of middle T antigen.
Conclusions:
- Middle T antigen's transformation activity is linked to its tyrosine phosphorylation.
- Growth factors, such as EGF, may regulate middle T antigen phosphorylation.
- This suggests a mechanism by which mitogenic signals control cellular transformation via polyoma virus proteins.
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