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Assessment of biological activity of synthetic fragments of transforming growth factor‐alpha
Author(s) -
Darlak Krzysztof,
Franklin Glen,
Woost Philip,
Sonnenfeld Elaine,
Twardzik Daniel,
Spatola Arno,
Schultz Gregory
Publication year - 1988
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.240360404
Subject(s) - autocrine signalling , transforming growth factor , dna synthesis , receptor , tgf alpha , peptide , dna , biological activity , chemistry , phosphorylation , biochemistry , biology , growth factor , microbiology and biotechnology , in vitro
Transforming growth factor‐alpha (TGF‐α) is a single chain polypeptide hormone of 50 amino acids that stimulates growth of some human cancer cells via an autocrine mechanism. The domain(s) of TGF‐α that bind and activate its receptor have not been reported. Hydrophilicity plots of TGF‐α indicate three discrete sequences that are theoretically exposed on the hormone's surface and thus potentially able to interact with the TGF‐α receptor. Fragments of TGF‐α encompassing these hydrophilic domains were prepared by using solid‐phase peptide synthesis (SPPS) techniques and purified by use of high performance liquid chromotography (HPLC). Assessment of biological activity of the TGF‐α fragments indicated that none of the fragments significantly inhibited binding of EOF to the receptor, stimulated DNA synthesis of cells, inhibited EGF‐induced DNA synthesis of cells, stimualted growth of cells in soft agar, or induced phosphorylation of the receptor or p35 protein. These results indicate that the receptor binding domain of TGF‐α is not totally encompassed by any of the separate fragments tested and probably is formed by multiple separate regions of TGF‐α.