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Cell-free activation of a DNA-binding protein by epidermal growth factor

Abstract

GROWTH factors such as platelet-derived growth factor and epidermal growth factor (EGF) bind to and activate cell-surface receptors with intrinsic tyrosine kinase activities1. Receptor activation elicits multiple physiological changes in target cells, including alterations in gene expression2–4. Receptor tyrosine kinase signalling involves recruitment of proteins into a signalling complex through interactions between receptor autophosphorylation sites and the src-homology region-2 (SH2) domains on these signalling proteins5–9. Diverse signals can subsequently be generated, depending on the specific receptor and cell type2,10. How such signals are transmitted to the nucleus is poorly understood, but because the transcriptional activation of many genes by growth factors occurs in the absence of new protein synthesis4, one or more signals emanating from growth factor receptors must directly affect transcription factors. We report here the activation by EGF of a DNA-binding protein in a cell-free system where activation of DNA binding requires ligand, receptor, ATP and phosphotyrosine–SH2 interactions.

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References

  1. Ullrich, A. & Schlessinger, J. Cell 61, 203–211 (1990).

    CAS  Article  Google Scholar 

  2. Rozengurt, E. Science 234, 161–166 (1986).

    ADS  CAS  Article  Google Scholar 

  3. Pardee, A. B. Science 246, 603–608 (1989).

    ADS  CAS  Article  Google Scholar 

  4. Herschman, H. R. An. Rev. Biochem. 60, 281–319 (1991).

    CAS  Article  Google Scholar 

  5. Williams, L. T. Science 243, 1564–1570 (1989).

    ADS  CAS  Article  Google Scholar 

  6. Kazlauskas, A. & Cooper, J. A. Cell 58, 1121–1133 (1989).

    CAS  Article  Google Scholar 

  7. Fantl, W. J. et al. Cell 69, 413–422 (1992).

    CAS  Article  Google Scholar 

  8. Koch, C. A., Anderson, D., Moran, M. F., Ellis, C. & Pawson, T. Science 252, 668–674 (1991).

    ADS  CAS  Article  Google Scholar 

  9. Margolis, B. Cell Growth Differ. 3, 73–80 (1992).

    CAS  PubMed  Google Scholar 

  10. Cantley, L. C. et al. Cell 64, 281–302 (1991).

    CAS  Article  Google Scholar 

  11. Greenberg, M. E. & Ziff, E. B. Nature 311, 433–437 (1984).

    ADS  CAS  Article  Google Scholar 

  12. Stumpo, D. J., & Blackshear, P. J. Proc. natn. Acad. Sci. U.S.A. 83, 9453–9457 (1986).

    ADS  CAS  Article  Google Scholar 

  13. Stumpo, D. J., Stewart, T. N., Gilman, M. Z. & Blackshear, P. J. J. biol. Chem. 263, 1611–1614 (1988).

    CAS  PubMed  Google Scholar 

  14. Gilman, M. Z. Genes Dev. 2, 394–402 (1988).

    CAS  Article  Google Scholar 

  15. Treisman, R. Semin. Cancer Biol. 1, 47–58 (1990).

    CAS  PubMed  Google Scholar 

  16. Wagner, B. J., Hayes, T. E., Hoban, C. J. & Cochran, B. H. EMBO J. 9, 4477–4484 (1990).

    CAS  Article  Google Scholar 

  17. Hayes, T. E., Kitchen, A. M. & Cochran, B. H. Proc. natn. Acad. Sci. U.S.A. 84, 1272–1276 (1987).

    ADS  CAS  Article  Google Scholar 

  18. Herrera, R. E., Shaw, P. E. & Nordheim, A. Nature 340, 68–70 (1989).

    ADS  CAS  Article  Google Scholar 

  19. Fabricant, R. N., Delarco, J. E. & Todaro, G. J. Proc. natn. Acad. Sci. U.S.A. 74, 565–569 (1977).

    ADS  CAS  Article  Google Scholar 

  20. Whittaker, J. et al. Proc. natn. Acad. Sci. U.S.A. 84, 5237–5241 (1987).

    ADS  CAS  Article  Google Scholar 

  21. Kanakura, Y. et al. Blood 76, 706–715 (1990).

    CAS  Article  Google Scholar 

  22. Field, J. et al. Molec. cell. Biol. 8, 2159–2165 (1988).

    CAS  Article  Google Scholar 

  23. Lowenstein, E. J. et al. Cell 70, 431–442 (1992).

    CAS  Article  Google Scholar 

  24. David, M. & Lamer, A. C. Science 257, 813–815 (1992).

    ADS  CAS  Article  Google Scholar 

  25. Fu, X.-Y. Cell 70, 323–335 (1992).

    CAS  Article  Google Scholar 

  26. Schindler, C., Shuai, K., Prezioso, V. R. & Darnell, J. E. J. Science 257, 809–812 (1992).

    ADS  CAS  Article  Google Scholar 

  27. Velazquez, L., Fellous, M., Stark, G. R. & Pellegrini, S. Cell 70, 313–322 (1992).

    CAS  Article  Google Scholar 

  28. Ryan, W. A., Franza, B. R. Jr & Gilman, M. Z. EMBO J. 8, 1785–1792 (1989).

    CAS  Article  Google Scholar 

  29. Dignam, J. D., Lebovitz, R. M. & Roeder, R. G. Nucleic Acids Res. 11, 1475–1489 (1983).

    CAS  Article  Google Scholar 

  30. Lee, K. A. W., Bindereif, A. & Green, M. R. Gene Anal. Techn. 5, 22–31 (1988).

    CAS  Article  Google Scholar 

Download references

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Sadowski, H., Gilman, M. Cell-free activation of a DNA-binding protein by epidermal growth factor. Nature 362, 79–83 (1993). https://doi.org/10.1038/362079a0

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