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Assessment of Resistance to Tyrosine Kinase Inhibitors by an Interrogation of Signal Transduction Pathways by Antibody Arrays
07:42

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Increased tyrosine kinase activity associated with the protein encoded by the activated neu oncogene

C I Bargmann1, R A Weinberg

  • 1Whitehead Institute for Biomedical Research, Nine Cambridge Center, MA 02142.

Proceedings of the National Academy of Sciences of the United States of America
|August 1, 1988
PubMed

Insights

A single mutation in the rat neu gene

Area of Science:

  • Oncogenesis
  • Molecular Biology
  • Signal Transduction

Background:

  • The rat neu gene encodes the receptor-like p185 protein.
  • A specific mutation in the transmembrane domain can convert the normal neu gene into a potent oncogene.
  • Understanding the biochemical changes associated with this oncogenic transformation is crucial.

Purpose of the Study:

  • To investigate the biochemical consequences of the oncogenic mutation in the p185 protein.
  • To compare the phosphorylation status of normal and transforming p185 molecules.
  • To determine if the transforming p185 protein possesses intrinsic kinase activity.

Main Methods:

  • Studying protein phosphorylation in membrane preparations.
  • In vitro biochemical assays to assess kinase activity.
  • Comparing phosphorylation levels between normal and mutated p185 proteins.

Main Results:

  • The transforming p185 protein exhibits significantly higher in vitro phosphorylation compared to the normal p185.
  • This enhanced phosphorylation occurs on tyrosine residues and requires functional p185 kinase activity.
  • Normal p185 does not show increased phosphorylation even in the presence of the transforming p185 within the same cell.

Conclusions:

  • The transforming p185 protein is intrinsically associated with active tyrosine kinase activity.
  • This active kinase function is directly linked to the mutation in the transmembrane domain.
  • The transmembrane domain of p185 plays a critical role in regulating its kinase activity and oncogenic potential.

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