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Abelson-transformed fibroblasts contain nuclear phosphotyrosyl-proteins which preferentially bind to murine DNA

Nature volume 325, pages 552–554 (1987)Cite this article

Abstract

Protein-tyrosine kinases, either in the form of growth-factor receptors1–3 or as the polypeptide products of oncogenes4,5, appear to be important in the regulation of cell growth and transformation. A major question, however, is how their substrates mediate changes in gene expression (reviewed in refs 6–8). Because binding of proteins to specific DNA sequences represents the most direct mechanism for regulating transcription, we have investigated the possibility that some DNA-binding proteins may be substrates of protein-tyrosine kinases. Here, we present evidence for nuclear phosphotyrosyl-proteins in murine fibroblasts transformed by the v-abl protein-tyrosine kinase. Furthermore, we have found that these proteins are not significantly phosphorylated in normal NIH 3T3 cells. Finally, using affinity competition chromatography with bacterial and mouse DNA, we have demonstrated that some of these proteins preferentially bind to mouse DNA. The identification of phosphotyrosyl-proteins with selective DNA-binding properties suggests a possible mechanism through which protein-tyrosine kinases may effect changes in gene transcription.

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Author notes

  1. John C. Bell

    Present address: Department of Biochemistry, McGill University, 3655 Drummond Street, Montreal, Quebec, H36 1Y6, Canada

  2. J. Gordon Foulkes: To whom correspondence should be addressed.

Authors and Affiliations

  1. Laboratory of Eukaryotic Molecular Genetics, National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK

    John C. Bell, Louis C. Mahadevan, William H. Colledge & J. Gordon Foulkes

  2. Laboratory of Embryogenesis, National Institute for Medical Research, Mill Hill, London, NW7 1AA, UK

    Michael G. Sargent

  3. Department of Medicine, Brown University, Roger Williams General Hospital, 825 Chalkstone Avenue, Providence, Rhode Island, 02908, USA

    A. Raymond Frackelton Jr

Authors
  1. John C. Bell
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  2. Louis C. Mahadevan
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  3. William H. Colledge
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  4. A. Raymond Frackelton Jr
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  5. Michael G. Sargent
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  6. J. Gordon Foulkes
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Bell, J., Mahadevan, L., Colledge, W. et al. Abelson-transformed fibroblasts contain nuclear phosphotyrosyl-proteins which preferentially bind to murine DNA. Nature 325, 552–554 (1987). https://doi.org/10.1038/325552a0

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