Analogs of human epidermal growth factor which partially inhibit the growth factor-dependent protein-tyrosine kinase activity of the epidermal growth factor 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-...

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Bibliographic Details
Published in:FEBS letters 1990-05, Vol.264 (1), p.105-108
Main Authors: Matsunami, Risë K., Campion, Stephen R., Niyogi, Salil K., Stevens, Audrey
Format: Article
Language:English
Subjects:
Analytical, structural and metabolic biochemistry
Binding, Competitive
Biological and medical sciences
Cell Line
Cell Membrane - metabolism
Competitive inhibitors of epidermal growth factor
DTT, 1,4-dithiothreitol
EOF, epidermal growth factor
Epidermal Growth Factor - genetics
Epidermal Growth Factor - metabolism
Epidermal Growth Factor - pharmacology
Epidermal growth factor analog
Epidermal growth factor receptor kinase
ErbB Receptors - metabolism
Fundamental and applied biological sciences. Psychology
hEGF, human epidermal growth factor
HPLC, high pressure liquid chromatography
Humans
Kinetics
Mutation
Protein hormones. Growth factors. Cytokines
protein-tyrosine kinase
Protein-Tyrosine Kinases - antagonists & inhibitors
Proteins
SDS, sodium dodecyl sulfate
V max, maximum velocity of a reaction
WGA, wheat germ agglutinin
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Summary: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.
ISSN:0014-5793
1873-3468
DOI:10.1016/0014-5793(90)80776-F