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Analogs of human epidermal growth factor which partially inhibit the growth factor‐dependent protein‐tyrosine kinase activity of the epidermal growth factor receptor
Author(s) -
Matsunami Risë K.,
Campion Stephen R.,
Niyogi Salil K.,
Stevens Audrey
Publication year - 1990
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(90)80776-f
Subject(s) - autophosphorylation , epidermal growth factor , tyrosine kinase , platelet derived growth factor receptor , growth factor receptor , growth factor receptor inhibitor , biology , tropomyosin receptor kinase c , grb2 , receptor tyrosine kinase , epidermal growth factor receptor , microbiology and biotechnology , signal transduction , biochemistry , chemistry , phosphorylation , growth factor , protein kinase a , receptor
Three site‐directed mutants of human epidermal growth factor, Leu‐26 → Gly, Leu‐47 → Ala, and He‐23 → Thr, were examined for their ability to stimulate the protein‐tyrosine kinase activity of the epidermal growth factor receptor. The receptor binding affinities of the mutant growth factors were 20‐ to 50‐fold lower, as compared to wild‐type growth factor. At saturating concentrations of growth factor, the velocities of the phosphorylation of exogenously added substrate and receptor autophosphorylation were significantly lower with the mutant analogs, suggesting a partial ‘uncoupling’ of signal transduction. The mutant analogs were shown to compete directly with the binding of wild‐type, resulting in a decrease in growth factor‐stimulated kinase activity.