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Phosphorylation of gastrin-17 by epidermal growth factor-stimulated tyrosine kinase

Abstract

Tyrosine phosphorylation seems to be a key event in the control of cellular growth. Several viral transforming proteins, including the src protein of Rous sarcoma virus1, the p120 protein of Abelson leukaemia virus2 and the middle T antigen of polyoma virus3, are phosphorylated by associated tyrosine kinases4–6. The levels of kinase activity correlate with the transforming efficiency of the virus6–8. The receptors for epidermal growth factor (EGF)9,10, platelet-derived growth factor (PDGF)11 and insulin12 are also phosphorylated by associated tyrosine kinase activities, which are stimulated by EGF, PDGF and insulin, respectively. The EGF-stimulated kinase13,14 and the src protein14,15 share similar substrate specificity for tyrosines immediately C-terminal to a sequence of acidic amino acids. Such a sequence is also found adjacent to the phosphotyrosine of middle T antigen16,17, and in the homologous region18 of the hormone gastrin, adjacent to a tyrosine which is sulphated in approximately half the gastrin isolated from gastric mucosa19. Reports that gastrin acts as a growth factor for cells of the gastrointestinal tract20 suggested that phosphorylation of this tyrosine might be physiologically more relevant than sulphation. We report here that synthetic human gastrin 17 is phosphorylated by the EGF-stimulated tyrosine kinase of A431 cell membranes. The Km values of 53–87 and 223–547 µM obtained in the presence and absence of EGF, respectively, are the lowest reported so far for this enzyme.

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Baldwin, G., Knesel, J. & Monckton, J. Phosphorylation of gastrin-17 by epidermal growth factor-stimulated tyrosine kinase. Nature 301, 435–437 (1983). https://doi.org/10.1038/301435a0

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