Abstract
Transforming growth factor- α (TGF- α) is a mitogenically active polypeptide hormone produced by acutely proliferating neoplastic and embryonic tissues1–4. Molecular cloning of TGF-α cDNA from human and rat has indicated that this factor is synthesized as part of a larger precursor, proTGF-α5,6. An intriguing feature of proTGF-α is that it contains a sequence of 24 hydrophobic amino acids following the bioactive TGF-α sequence. Similar hydrophobic sequences present in transmembrane proteins are cotranslationally anchored into the phospholipid bilayer of the rough endoplasmic reticulum7,8, suggesting the possibility that proTGF-α might be an integral membrane protein. Other secretory proteins including all known prohormones lack membrane anchoring sequences and are completely translocated across the endoplasmic reticulum membrane7,8. To address the question of whether proTGF-α is as an integral membrane protein we have translated rat proTGF-α mRNA transcripts in the presence of rough endoplasmic reticulum membrane vesicles. The results indicate that proTGF-α is synthesized as an integral membrane glycoprotein. The 50-amino-acid TGF-α sequence in proTGF-α is exposed to the fluid extracellular phase where it can be released after cleavage by the appropriate enzyme.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Marquardt, H. et al. Proc. natn. Acad. Sci. U.S.A. 80, 4684–4688 (1983).
Massagué, J. J. biol. Chem. 258, 13607–13613 (1983).
Todaro, G. J., Fryling, C. & DeLarco, J. E. Proc. natn. Acad. Sci. U.S.A. 77, 5258–5262 (1980).
Twardzik, D. R. Cancer Res. 45, 5413–5416 (1980).
Derynck, R., Roberts, A. B., Winkler, M. E., Chen, E. Y. & Goeddel, D. V. Cell 38, 287–297 (1984).
Lee, D. C., Rose, T. M., Webb, N. R. & Todaro, G. J. Nature 313, 489–491 (1985).
Blobel, G. Proc. natn. Acad. Sci. U.S.A. 77, 1496–1500 (1980).
Sabatini, D. D., Kreibich, G., Morimoto, T. & Adesnik, M. J. Cell Biol. 92, 1–22 (1982).
Ignotz, R. A., Kelly, B., Davis, R. J. & Massagué, J. Proc. natn. Acad. Sci. U.S.A. 83, 6307–6311 (1986).
Evans, E. A., Gilmore, R. & Blobel, G. Proc. natn. Acad. Sci. U.S.A. 83, 581–585 (1986).
Rothman, J. E. & Lodish, H. F. Nature 269, 775–780 (1977).
Von Heijne, G. Eur. J. Biochem. 133, 17–21 (1983).
Fujiki, Y., Fowler, S., Shio, H., Hubbard, A. & Lazarov, P. J. Cell Biol. 93, 103–119 (1982).
Von Heijne, G. J. molec. Biol. 173, 243–251 (1984).
Gray, A., Dull, T. J. & Ullrich, A. Nature 303, 722–725 (1983).
Scott, J. et al. Science 221, 236–240 (1983).
Blomquist, M. C., Hunt, L. T. & Barker, W. C. Proc. natn. Acad. Sci. U.S.A. 81, 7363–7367 (1984).
Stroobant, P. Cell 42, 383–393 (1985).
Wharton, K. A., Johansen, K. M., Xu, T. & Artavanis-Tsakonas, S. Cell 43, 567–581 (1985).
Bell, G. I. et al. Nucleic Acids Res. 14, 8427–8446 (1986).
Connolly, T. & Gilmore, R. J. Cell Biol. 103, 2253–2261 (1986).
Erickson, A. H. & Blobel, G. Meth. Enzym. 96, 84–93 (1983).
Walter, P., Ibrahimi, I. & Blobel, G. J. Cell Biol. 91, 545–550 (1981).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Teixidó, J., Gilmore, R., Lee, D. et al. Integral membrane glycoprotein properties of the prohormone pro-transforming growth factor-α. Nature 326, 883–885 (1987). https://doi.org/10.1038/326883a0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/326883a0
This article is cited by
-
Altered proTGFα/cleaved TGFα ratios offer new therapeutic strategies in renal carcinoma
Journal of Experimental & Clinical Cancer Research (2021)
-
Signal peptidase complex 18, encoded by SEC11A, contributes to progression via TGF-α secretion in gastric cancer
Oncogene (2014)
-
Proteolytic maturation of transforming growth factor-α
Perspectives in Drug Discovery and Design (1995)
-
Characterization of liver epithelial cells transfected withmyc and/orras oncogenes
Digestive Diseases and Sciences (1991)
Comments
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.