Letter | Published:

Re-routing of a secretory protein by fusion with human growth hormone sequences

Naturevolume 321pages443446 (1986) | Download Citation



Cells with electron-dense secretory vesicles use them to store only specialized secretory products such as peptide hormones; other types of secreted proteins are externalized by an alternative, constitutive route1. One possible mechanism for such segregation is that proteins destined for dense secretory vesicles contain unique ‘sorting domains’2 that allow for selective targeting. Here, we set out to determine whether a constitutively secreted protein could be diverted to the dense secretory vesicles by attachment to a peptide hormone sequence. We made use of the ability of the mouse pituitary tumour cell line, AtT-20, to correctly sort exogenous secretory proteins introduced into them by DNA transfection3. We constructed a plasmid encoding a hybrid protein in which a constitutively secreted viral protein was fused to the carboxy terminus of human growth hormone (hGH). Cells expressing the hybrid protein were found to target it to dense secretory vesicles with an efficiency close to that observed for the parental hGH. These results support the hypothesis that sorting domains on peptide hormones direct their packaging into dense secretory vesicles. The results also suggest that proteins secreted by the constitutive pathway either do not contain any sorting domain, or their sorting signals can be overridden by those which direct peptide hormones.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1

    Kelly, R. B. Science 230, 25–32 (1985).

  2. 2

    Blobel, G. Proc. natn. Acad. Sci. U.S.A. 77, 1496–1500 (1980).

  3. 3

    Moore, H.-P. H. & Kelly, R. B. J. Cell Biol. 101, 1773–1781 (1985).

  4. 4

    Hall, M. N., Hereford, L. & Herskowitz, I. Cell 36, 1057–1065 (1984).

  5. 5

    Emr, S. D., Bankaitis, V. A., Garrett, J. M. & Douglas, M. G. in Protein Transport and Secretion (ed. Gething, M.-J.) (Cold Spring Harbor Laboratory, New York, 1985).

  6. 6

    Hurt, E. C., Pesold-Hurt, B. & Schatz, G. EMBO J. 3, 3149–3156 (1984).

  7. 7

    Silhavy, T. J. & Beckwith, J. Meth. Enzym. 97, 11–40 (1983).

  8. 8

    Doyle, C., Roth, M., Sambrook, J. & Gething, M.-J. J. Cell Biol. 100, 704–714 (1985).

  9. 9

    Guan, J.-L., Machamer, C. E. & Rose, J. K. Cell 42, 489–496 (1985).

  10. 10

    Rose, J. K. & Bergmann, J. E. Cell 30, 753–762 (1982).

  11. 11

    Martial, J. A., Hallewell, R. A., Baxter, J. D. & Goodman, H. M. Science 205, 602–607 (1979).

  12. 12

    Moore, H. P., Gumbiner, B. & Kelly, R. B. J. Cell Biol. 97, 810–817 (1983).

  13. 13

    Moore, H.-P. H., Gumbiner, B. & Kelly, R. B. Nature 302, 434–436 (1983).

  14. 14

    Neufeld, E. F., Lim, T. W. & Shapiro, L. J. AZ. Rev. Biochem. 44, 357–376 (1975).

  15. 15

    Lodish, H. F., Kong, N., Snider, M. & Strous, G. J. A. M. Nature 304, 80–83 (1983).

  16. 16

    Fries, E., Gustafsson, L. & Peterson, P. A. EMBO J. 3, 147–152 (1984).

  17. 17

    Firestone, G. L. J. biol. Chem. 258, 6155–6161 (1983).

  18. 18

    Sanger, F., Nicklen, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

Download references

Author information


  1. Department of Physiology-Anatomy, University of California, Berkeley, California, 94720, USA

    • Hsiao-ping H. Moore
  2. Department of Biochemistry and Biophysics, University of California, San Francisco, California, 94143, USA

    • Regis B. Kelly


  1. Search for Hsiao-ping H. Moore in:

  2. Search for Regis B. Kelly in:

About this article

Publication history



Issue Date



Further reading


By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.