Cloning and sequence analysis of a cDNA for rat transforming growth factor-α (original) (raw)
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- Published: 07 February 1985
Nature volume 313, pages 489–491 (1985)Cite this article
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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-_α_s 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-_α_4 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-_α_s belong to a family of EGF-like polypeptides7. TGF-_β_s, on the other hand, display no measurable binding to EGF receptors, but potentiate the growth stimulating activities of TGF-_α_8. 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.
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Authors and Affiliations
- Oncogen, 3005 First Avenue, Seattle, Washington, 98121, USA
David C. Lee, Timothy M. Rose, Nancy R. Webb & George J. Todaro - Department of Pathology, University of Washington, School of Medicine, Seattle, Washington, 98195, USA
George J. Todaro
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- David C. Lee
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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: 01 August 1984
- Accepted: 07 November 1984
- Issue Date: 07 February 1985
- DOI: https://doi.org/10.1038/313489a0