Abstract
TRIGGERING of mast cells and basophils by immunoglobulin E (IgE) and antigen induces various biochemical signals, including tyrosine kinase activation1,2, which lead to cell degranulation and the release of mediators of the allergic reaction. The high-affinity receptor for IgE (FcσRI) responsible for initiating these events is a complex structure composed of an IgE-binding α-chain, a β-chain and a homodimer of γ-chains3. It has been assumed that β and γ, which have extensive cytoplasmic domains, play an important but undefined role in coupling FcσRI to signal transduction mechanisms. Here we show that FcσRI engagement induces immediate in vivo phosphorylation on β(tyrosine and serine) and γ (tyrosine and threonine) by at least two different non-receptor kinases. We take advantage of unique features of this receptor system to demonstrate that the phosphorylation signal is restricted to activated receptors and is immediately reversible upon receptor disengagement by undefined phosphatases. Rapid phosphorylation and dephosphorylation may be a general mechanism to couple and uncouple activated receptors to other effector molecules. This could be particularly relevant to other multimeric receptors containing Fcσ RI γ-chains or the related ζ and η chains such as the T-cell antigen receptor (TCR)4–6 and the low-affinity receptor for immunoglobulin G (FcγRIII, CD16) (refs 7–11).
Similar content being viewed by others
References
Benhamou, M., Gutkind, J. S., Robbins, K. C. & Siraganian, R. P. Proc. natn. Acad. Sci. U.S.A. 87, 5327–5330 (1990).
Connelly, P. A., Farrel, C. A., Merenda, J. M., Conklyn, M. J. & Showell, H. J. Biochem. biophys. Res. Commun. 177, 192–201 (1991).
Blank, U. et al. Nature 337, 187–189 (1989).
Weissman, A. M. et al. Science 239, 1018–1021 (1988).
Jin, Y. J. et al. Proc. natn. Acad. Sci. U.S.A. 87, 3319–3323 (1990).
Orloff, D. G., Ra, C., Frank, S. J., Klausner, R. D. & Kinet, J.-P. Nature 347, 189–191 (1990).
Ra, C., Jouvin, M.-H. E., Blank, U. & Kinet, J.-P. Nature 341, 752–754 (1989).
Hibbs, M. L. et al. Science 246, 1608–1611 (1989).
Kurosaki, T. & Ravetch, J. V. Nature 342, 805–807 (1989).
Anderson, P. et al. Proc. natn. Acad. Sci. U.S.A. 87, 2274–2278 (1990).
Lanier, L. L., Yu, G. & Phillips, J. H. Nature 342, 803–804 (1989).
Rivera, J., Kinet, J.-P., Kim, J., Pucillo, C. & Metzger, H. Molec. Immun. 25, 647–661 (1988).
Perez-Montfort, R., Fewtrell, C. & Metzger, H. Biochemistry 22, 5733–5737 (1983).
Quarto, R. & Metzger, H. Molec. Immun. 23, 1215–1223 (1986).
Millard, P. J., Gross, D., Webb, W. W. & Fewtrell, C. Proc. natn. Acad. Sci. U.S.A. 85, 1854–1858 (1988).
Cunha-Melo, J. R., Dean, N. M., Moyer, J. D., Maeyama, K. & Beaven, M. A. J. biol. Chem. 262, 11455–11463 (1987).
Basciano, L. K., Berenstein, E. H., Kmak, L. & Siraganian, R. P. J. biol. Chem. 261, 11823–11831 (1986).
Klausner, R. D. & Samelson, L. E. Cell 64, 875–878 (1991).
Lane, P. J. L. et al. J. Immun. 146, 715–722 (1991).
Baniyash, M., Garcia-Morales, P., Luong, E., Samelson, L. E. & Klausner, R. D. J. biol. Chem. 263, 18225–18230 (1988).
O'Shea, J. J., Weissman, A. M., Kennedy, I. C. S. & Ortaldo, J. R. Proc. natn. Acad. Sci. U.S.A. 88, 350–354 (1991).
Vivier, E. et al. J. Immun. 146, 206–210 (1991).
Irving, B. A. & Weiss, A. Cell 64, 891–901 (1991).
Stephan, V. et al. FASEB J. 5, abst. 7578 (1991).
Eiseman, E. & Bolen, J. Cancer Cells 2, 303–310 (1990).
Liu, F. T. et al. J. Immun. 124, 2728–2737 (1980).
Cooper, J. A., Sefton, B. M. & Hunter, T. Meth. Enzym. 99, 387–402 (1983).
Druker, B. J., Manon, H. J. & Roberts, T. M. New Engl. J. Med. 321, 1383–1391 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Paolini, R., Jouvin, MH. & Kinet, JP. Phosphorylation and dephosphorylation of the high-affinity receptor for immunoglobulin E immediately after receptor engagement and disengagement. Nature 353, 855–858 (1991). https://doi.org/10.1038/353855a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/353855a0
- Springer Nature Limited
This article is cited by
-
The role of FcεRI expressed in dendritic cells and monocytes
Cellular and Molecular Life Sciences (2015)
-
Integrated signalling pathways for mast-cell activation
Nature Reviews Immunology (2006)
-
A role for epithelial γδ T cells in tissue repair
Springer Seminars in Immunopathology (2000)
-
Signalling through the high-affinity IgE receptor FcεRI
Nature (1999)