Analogs of human epidermal growth factor which partially inhibit the growth factor-dependent protein-tyrosine kinase activity of the epidermal growth factor receptor |
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Authors: | R K Matsunami S R Campion S K Niyogi A Stevens |
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Institution: | Protein Engineering and Molecular Mutagenesis Program, Oak Ridge National Laboratory, TN 37831-8077. |
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Abstract: | Three site-directed mutants of human epidermal growth factor, Leu-26----Gly, Leu-47----Ala, and Ile-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. |
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