Analogs of human epidermal growth factor which partially inhibit the growth factor‐dependent protein‐tyrosine kinase activity of the epidermal growth factor receptor

FEBS Letters

Campion, Stephen R.¹  Stevens, Audrey¹  Niyogi, Salil K.¹  Matsunami, Risë K.¹ 

[1] Protein Engineering and Molecular Mutagenesis Program and the University of Tennessee-Oak Ridge Graduate School of Biomedical Sciences. Biology Division, Oak Ridge National Laboratory. Oak Ridge, TN 37831-8077, USA

关键词: Epidermal growth factor analog;    Epidermal growth factor receptor kinase;    Competitive inhibitors of epidermal growth factor;    EOF;    epidermal growth factor;    hEGF;    human epidermal growth factor;    DTT;    1;    4-dithiothreitol;    WGA;    wheat germ agglutinin;    HPLC;    high pressure liquid chromatography;    V max;    maximum velocity of a reaction;    SDS;    sodium dodecyl sulfate;   

DOI  :  10.1016/0014-5793(90)80776-F

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown