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.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Czernilofsky, A. P. et al. Nature 287, 198–203 (1980).
Witte, O. N., Rosenberg, N., Paskind, M., Shields, A. & Baltimore, D. Proc. natn. Acad. Sci. U.S.A. 75, 2488–2492 (1978).
Soeda, E., Arrand, J. R., Smolar, N. & Griffin, B. E. Cell 17, 357–370 (1979).
Hunter, T. & Sefton, B. M. Proc. natn. Acad. Sci. U.S.A. 77, 1311–1315 (1980).
Witte, O. N., Dasgupta, A. & Baltimore, D. Nature 283, 826–831 (1980).
Turler, H. Molec. cell. Biochem. 32, 63–93 (1980).
Collett, M. S. & Erikson, R. L. Proc. natn. Acad. Sci. U.S.A. 75, 2021–2024 (1978).
Witte, O. N., Goff, S., Rosenberg, N. & Baltimore, D. Proc. natn. Acad. Sci. U.S.A. 77, 4993–4997 (1980).
Carpenter, G., King, L. & Cohen, S. J. biol. Chem. 254, 4884–4891 (1979).
Cohen, S., Carpenter, G. & King, L. J. biol. Chem. 255, 4834–4842 (1980).
Nishimura, J., Huang, J. S. & Deuel, T. F. Proc. natn. Acad. Sci. U.S.A. 79, 4303–4307 (1982).
Kasuga, M., Zick, Y., Blithe, D. L., Crettaz, M. & Kahn, C. R. Nature 298, 667–669 (1982).
Pike, L. J., Gallis, B., Casnellie, J. E., Bornstein, P. & Krebs, E. G. Proc. natn. Acad. Sci. U.S.A. 79, 1443–1447 (1982).
Hunter, T. J. biol. Chem. 257, 4843–4848 (1982).
Smart, J. E. et al. Proc. natn. Acad. Sci. U.S.A. 78, 6013–6017 (1981).
Neil, J. C., Ghysdael, J., Vogt, P. K. & Smart, J. C. Nature 291, 675–677 (1981).
Schaffhausen, B. & Benjamin, T. L. J. Virol. 40, 184–196 (1981).
Baldwin, G. S. FEBS Lett. 137, 1–5 (1982).
Gregory, R. A. & Tracy, H. J. Gut 5, 103–117 (1964).
Johnson, L. R. Gastroenterology 70, 278–288 (1976); 72, 788–792 (1977).
Brautigan, D. L., Bornstein, P. & Gallis, B. J. biol Chem. 256, 6519–6522 (1981).
Baldwin, G. S., Burgess, A. W. & Kemp, B. E. Biochem. biophys. Res. Commun. (in the press).
Takeuchi, K., Speir, G. R. & Johnson, L. R. Am. J. Physiol. 239, G395–399 (1980).
Carter, D. C., Taylor, I. L., Elashoff, J. & Grossman, M. I. Gut 20, 705–708 (1979).
Johnson, L. R. & Guthrie, P. D. Gastroenterology 71, 599–602 (1976).
Jensen, R. T., Lemp, G. F. & Gardner, J. D. J. biol. Chem. 257, 5554–5559 (1982).
Johnson, L. R., Stening, G. F. & Grossman, M. I. Gastroenterology 58, 208–216 (1970).
Burgess, A. W., Knesel, J., Sparrow, L. G., Nicola, N. A. & Nice, E. C. Proc. natn. Acad. Sci. U.S.A. 79, 5753–5757 (1982).
Kemp, B. E. J. biol. Chem. 254, 2638–2642 (1979).
McGuigan, J. E. & Wolfe, M. M. Clin. Chem. 28, 368–373 (1982).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
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
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/301435a0
This article is cited by
-
Phosphopeptidomics Reveals Differential Phosphorylation States and Novel SxE Phosphosite Motifs of Neuropeptides in Dense Core Secretory Vesicles
Journal of the American Society for Mass Spectrometry (2018)
-
Tyrosine modification increases the affinity of gastrin for ferric ions
SpringerPlus (2015)
-
Complete tyrosine-O-sulphation of gastrin in neonatal rat pancreas
Nature (1984)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.