Abstract
Transforming growth factors (TGFs) are mitogenic polypeptides produced most conspicuously by transformed cells and conferring on normal cells several phenotypic alterations associated with transformation1,2. TGFs comprise two distinct sets of molecules: TGF-αs are structurally similar to epidermal growth factor (EGF), binding to and inducing the tyrosine phosphorylation of the EGF receptor in a manner indistinguishable from that of EGF3. In addition, the 50-amino acid rat TGF-α4 has 33 and 44% homologies with mouse5 and human6 EGFs, respectively, and shares with EGFs a conserved pattern of three disulphide bridges7. Thus, it has been proposed that TGF-αs belong to a family of EGF-like polypeptides7. TGF-βs, on the other hand, display no measurable binding to EGF receptors, but potentiate the growth stimulating activities of TGF-α8. Here we report the isolation of a complementary DNA clone encoding rat TGF-α. This cDNA hybridizes to a 4.5-kilobase (kb) messenger RNA that is 30 times larger than necessary to code for a 50-amino acid polypeptide and is present not only in retrovirus-transformed rat cells but also at lower levels in normal rat tissues. The nucleotide sequence of the cDNA predicts that TGF-α is synthesized as a larger product and that the larger form may exist as a transmembrane protein. However, unlike many polypeptide hormones (including EGF9,10), cleavage of the 50-amino acid TGF-α from the larger form does not occur at paired basic residues, but rather between alanine and valine residues, suggesting the role of a novel protease.
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
Todaro, G. J., DeLarco, J. E., Fryling, C., Johnson, P. A. & Sporn, M. B. J. supramolec. Struct. 15, 287–301 (1981).
DeLarco, J. E. & Todaro, G. J. Proc. natn. Acad. Sci. U.S.A. 75, 4001–4005 (1978).
Pike, L. J. et al. J. biol. Chem. 257, 14628–14631 (1983).
Marquardt, H. et al. Proc. natn. Acad. Sci. U.S.A. 80, 4684–4688 (1983).
Savage, C. R. Jr, Inagami, T. & Cohen, S. J. biol. Chem. 247, 7612–7621 (1972).
Gregory, H. Nature 257, 325–327 (1975).
Marquardt, H., Hunkapiller, H. W., Hood, L. E. & Todaro, G. J. Science 223, 1079–1082 (1984).
Anzano, M. A. et al. Cancer Res. 42, 4776–4778 (1982).
Gray, A., Dull, T. J. & Ullrich, A. Nature 303, 722–725 (1983).
Scott, J. et al. Science 221, 236–240 (1983).
Twardzik, D. R., Todaro, G. J., Reynolds, F. H. Jr & Stephenson, J. R. Virology 124, 201–207 (1983).
Huynh, T., Young, R. & Davis, R. in Practical Approaches in Biochemistry (ed. Glover, D.) (IRL, Oxford, 1984).
Dente, L., Cesareni, G. & Cortese, R. Nucleic Acids Res. 11, 1645–1655 (1983).
Linsley, P. S., Hargreaves, W. R., Twardzik, D. R. & Todaro, G. J. Proc. natn. Acad. Sci. U.S.A. (in the press).
Naughton, M. A. & Sanger, F. Biochem. J. 78, 156–162 (1961).
Matsubara, H. Meth. Enzym. 19, 642–651 (1970).
Kreil, G. A. Rev. Biochem. 50, 317–348 (1981).
Okayama, H. & Berg, P. Molec. cell. Biol. 2, 161–167 (1982).
Smith, A. J. H. Meth. Enzym. 65, 560–580 (1980).
Glisin, V., Crkvenjakov, R. & Byns, C. Biochemistry 13, 2633–2638 (1974).
Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J. & Rutter, W. J. Biochemistry 18, 5294–5299 (1979).
Maniatis, T., Fritsch, E. F. & Sambrook, J. in Molecular Cloning (Cold Spring Harbor Laboratory, New York, 1982).
Southern, E. M. J. molec. Biol. 98, 503–517 (1975).
Brown, J. P., Twardzik, D. R., Marquardt, H. & Todaro, G. J. Nature 313, 491–492 (1985).
Derynck, R., Roberts, A. B., Winkler, M. E., Chen, E. Y. & Goeddel, D. V. Cell 38, 287–297 (1984).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lee, D., Rose, T., Webb, N. et al. Cloning and sequence analysis of a cDNA for rat transforming growth factor-α. Nature 313, 489–491 (1985). https://doi.org/10.1038/313489a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/313489a0
This article is cited by
-
Signal peptidase complex 18, encoded by SEC11A, contributes to progression via TGF-α secretion in gastric cancer
Oncogene (2014)
-
Defective cleavage of membrane bound TGFα leads to enhanced activation of the EGF receptor in malignant cells
Oncogene (2000)
-
Roles of transforming growth factor-α and related molecules in the nervous system
Molecular Neurobiology (1999)
-
Characterization of the mouse Tdgf1 gene and Tdgf pseudogenes
Mammalian Genome (1996)
-
Enhanced gene expression of transforming growth factor-? and c-met in rat urinary bladder cancer
Urological Research (1996)
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.