Cloning and sequence analysis of a cDNA for rat transforming growth factor-α

David C. Lee, Timothy M. Rose, Nancy R. Webb, George J. Todaro

Research output: Contribution to journalArticlepeer-review

274 Scopus citations

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.

Original languageEnglish
Pages (from-to)489-491
Number of pages3
JournalNature
Volume313
Issue number6002
DOIs
StatePublished - 1985

ASJC Scopus subject areas

  • General

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