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Phosphatidylinositol kinases and cell transformation
L Cantley1, M Whitman, D R Kaplan
1Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111.
Symposium on Fundamental Cancer Research
|January 1, 1986
Summary
Viral oncogenes regulate cell growth by altering phosphatidylinositol (PI) turnover. A specific PI kinase associates with viral middle T oncoproteins, suggesting a role in cell transformation.
Area of Science:
- Cell Biology
- Molecular Oncology
- Biochemistry
Background:
- Phosphatidylinositol (PI) turnover products regulate cell growth and differentiation.
- Viral oncogenes and transforming proteins alter PI turnover pathways.
- Polyoma middle T oncoprotein complexes with cellular enzymes.
Purpose of the Study:
- Investigate the role of PI turnover in viral transformation.
- Identify cellular enzymes associated with viral oncoproteins.
- Characterize PI kinases involved in cell transformation.
Main Methods:
- Cell culture and viral infection/transfection.
- Immunoprecipitation of viral oncoproteins.
- Enzyme assays for PI kinase activity.
- Anion exchange chromatography for enzyme purification.
Main Results:
- Viral transformation affects PI turnover intermediates.
- Polyoma middle T immunoprecipitates show PI kinase activity.
- A specific type I PI kinase associates with transformation-competent middle T mutants.
- Two PI kinases (Type I and II) with different kinetic properties were identified.
Conclusions:
- The association of PI kinase with viral middle T oncoproteins is crucial for cell transformation.
- Type I PI kinase is specifically implicated in the transformation process.
- Viral oncogenes utilize cellular PI kinases to modulate cell growth and differentiation.