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Nuclear accumulation of epidermal growth factor in cultured rat pituitary cells

Naturevolume 287pages340343 (1980) | Download Citation

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Abstract

Epidermal growth factor (EGF) is a mitogen for epidermal cells in vivo1,2 and for a wide variety of cells in culture3–5. Recently, we and others have reported that EGF can also regulate the cellular levels of various hormones6 and fibronectin7 at concentrations which only minimally influence cell division. In addition, EGF treatment of GH3 cells affects chromatin structure such that isolated nuclei from treated cells have an increased capacity to bind bacterial RNA polymerase in initiation site complexes6. Thus, the data suggest that various nuclear functions are modulated by EGF in GH3 cells despite its failure to affect DNA synthesis or cell proliferation. Recently, Yanker and Shooter8 have reported on the nuclear accumulation of nerve growth factor (NGF) in PC12 cells in which NGF does not promote cell division but does influence RNA and protein synthesis while inducing overt differentiation (neurite outgrowth). The similarities between the two systems and the various theories regarding the mechanism by which mitogens exert their growth-promoting and other effects9,10 led us to investigate whether an interaction between EGF and the cell nucleus can be demonstrated after surface binding and internalization of EGF in GH3 cells. We report here that when its lysosomal degradation is inhibited by chloroquine, EGF accumulates in the nucleus.

References

  1. 1

    Birnbaum, J. E., Sapp, T. M. & Moore, J. B. J. invest. Derm. 66, 313–318 (1976).

  2. 2

    Savage, C. R. & Cohen, S. Expl Eye Res. 15, 361–366 (1973).

  3. 3

    Rheinwald, J. G. & Green, H. Nature 265, 421–242 (1977).

  4. 4

    Gospodarowicz, D., Ill, C. R. & Birdwell, C. R. Endocrinology 100, 1108–1115 (1977).

  5. 5

    Savage, C. R. & Cohen, S. J. biol. Chem. 247, 7609–7611 (1972).

  6. 6

    Johnson, L. K., Baxter, J. D., Vlodavsky, I. & Gospodarowicz, D. Proc. natn. Acad. Sci. U.S.A. 77, 394–398 (1980).

  7. 7

    Chen, L. B., Guoor, R. C., Sun, T. T., Chen, A. B. & Mosesson, M. W. Science 197, 776–778 (1977).

  8. 8

    Yanker, B. A. & Shooter, E. M. Proc. natn. Acad. Sci. U.S.A. 76, 1269–1273 (1979).

  9. 9

    Carpenter, G. & Cohen, S. A. Rev. Biochem. 48, 193–226 (1979).

  10. 10

    Das, M. & Fox, F. C. Proc. natn. Acad. Sci. U.S.A. 75, 2644–2648 (1978).

  11. 11

    Carpenter, G., Lembach, K., Morrison, M. & Cohen, S. J. biol. Chem. 250, 4297–4304 (1975).

  12. 12

    Carpenter, G. & Cohen, S. J. Cell Biol. 71, 159–171 (1976).

  13. 13

    Brandenberger, H. & Hanson, R. Helv. chim. Acta 36, 900–904 (1953).

  14. 14

    Jackson, P. C. Biochemistry 15, 5641–5651 (1976).

  15. 15

    Adolph, K. W., Chang, S. M. & Laemmli, U. K. Cell 12, 805–812 (1977).

  16. 16

    Laemmli, U. K. et al. Cold Spring Harb. Symp. quant. Biol. 42, 351–360 (1977).

  17. 17

    Levy, B. W. & Baxter, J. D. Biochem. biophys. Res. Commun. 68, 1045–1051 (1976).

  18. 18

    Charles, M. A., Ryffel, G. W., Obinata, M., McCarthy, B. J. & Baxter, J. D. Proc. natn. Acad. Sci. U.S.A. 72, 1787–1791 (1975).

  19. 19

    Samuels, H. H., Stanley, F. & Shapiro, L. J. biol. Chem. 252, 6052–6060 (1977).

  20. 20

    Goidl, J. A. Biochemistry 18, 3674–3678 (1979).

  21. 21

    Haigier, H., Ash, J. F., Singer, S. J. & Cohen, S. Proc. natn. Acad. Sci. U.S.A. 75, 3317–3321 (1978).

  22. 22

    Szego, C. J. Recent Prog. Horm. Res. 30, 171–233 (1974).

  23. 23

    Savion, N., Vlodavsky, I. & Gospodarowicz, D. Proc. natn. Acad. Sci. U.S.A. 77, 1466–1470 (1980).

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Affiliations

  1. Howard Hughes Medical Institute Laboratories, Endocrine Research Division, University of California, San Francisco, California, 94143

    • L. K. Johnson
    •  & J. D. Baxter
  2. Howard Hughes Medical Institute Laboratories, Cancer Research Institute and the Department of Medicine, University of California, San Francisco, California, 94143

    • I. Vlodavsky
    •  & D. Gospodarowicz

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https://doi.org/10.1038/287340a0

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