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
PubMed

Insights

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.

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