Skip to main content
PMC home page
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1994 Aug;14(8):5108–5113. doi: 10.1128/mcb.14.8.5108

Tyrosine phosphorylation and activation of Bruton tyrosine kinase upon Fc epsilon RI cross-linking.

Y Kawakami 1, L Yao 1, T Miura 1, S Tsukada 1, O N Witte 1, T Kawakami 1
PMCID: PMC359029  PMID: 7518558

Abstract

Tyrosine phosphorylation of several cellular proteins is one of the earliest signaling events induced by cross-linking of the high-affinity receptor for immunoglobulin E (Fc epsilon RI) on mast cells or basophils. Tyrosine kinases activated during this process include the Src family kinases, Lyn, c-Yes, and c-Src, and members of another subfamily, Syk and PTK72 (identical or highly related to Syk). Recently, some of us described two novel tyrosine kinases, Emb and Emt, whose expression was limited to subsets of hematopoietic cells, including mast cells. Emb turned out to be identical to Btk, a gene product defective in human X-linked agammaglobulinemia and in X-linked immunodeficient (xid) mice. Here we report that Fc epsilon RI cross-linking induced rapid phosphorylation on tyrosine, serine, and threonine residues and activation of Btk in mouse bone marrow-derived mast cells. A small fraction of Btk translocated from the cytosol to the membrane compartment following receptor cross-linking. Tyrosine phosphorylation of Btk was not induced by either a Ca2+ ionophore (A23187), phorbol 12-myristate 13-acetate, or a combination of the two reagents. Co-immunoprecipitation between Btk and receptor subunit beta or gamma was not detected. The data collectively suggest that Btk is not associated with Fc epsilon but that its activation takes place prior to protein kinase C activation and plays a novel role in the Fc epsilon RI signaling pathway.

Full text

PDF
5108

Images in this article

5110Image
on p.5110
5110Image
on p.5110
5111Image
on p.5111
5111Image
on p.5111
5112Image
on p.5112

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Atkinson T. P., Kaliner M. A., Hohman R. J. Phospholipase C-gamma 1 is translocated to the membrane of rat basophilic leukemia cells in response to aggregation of IgE receptors. J Immunol. 1992 Apr 1;148(7):2194–2200. [PubMed] [Google Scholar]
  2. Benhamou M., Gutkind J. S., Robbins K. C., Siraganian R. P. Tyrosine phosphorylation coupled to IgE receptor-mediated signal transduction and histamine release. Proc Natl Acad Sci U S A. 1990 Jul;87(14):5327–5330. doi: 10.1073/pnas.87.14.5327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Benhamou M., Ryba N. J., Kihara H., Nishikata H., Siraganian R. P. Protein-tyrosine kinase p72syk in high affinity IgE receptor signaling. Identification as a component of pp72 and association with the receptor gamma chain after receptor aggregation. J Biol Chem. 1993 Nov 5;268(31):23318–23324. [PubMed] [Google Scholar]
  4. Benhamou M., Stephan V., Robbins K. C., Siraganian R. P. High-affinity IgE receptor-mediated stimulation of rat basophilic leukemia (RBL-2H3) cells induces early and late protein-tyrosine phosphorylations. J Biol Chem. 1992 Apr 15;267(11):7310–7314. [PubMed] [Google Scholar]
  5. Chen R. H., Sarnecki C., Blenis J. Nuclear localization and regulation of erk- and rsk-encoded protein kinases. Mol Cell Biol. 1992 Mar;12(3):915–927. doi: 10.1128/mcb.12.3.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Conley M. E. Molecular approaches to analysis of X-linked immunodeficiencies. Annu Rev Immunol. 1992;10:215–238. doi: 10.1146/annurev.iy.10.040192.001243. [DOI] [PubMed] [Google Scholar]
  7. Connelly P. A., Farrell C. A., Merenda J. M., Conklyn M. J., Showell H. J. Tyrosine phosphorylation is an early signaling event common to Fc receptor crosslinking in human neutrophils and rat basophilic leukemia cells (RBL-2H3). Biochem Biophys Res Commun. 1991 May 31;177(1):192–201. doi: 10.1016/0006-291x(91)91967-h. [DOI] [PubMed] [Google Scholar]
  8. Eiseman E., Bolen J. B. Engagement of the high-affinity IgE receptor activates src protein-related tyrosine kinases. Nature. 1992 Jan 2;355(6355):78–80. doi: 10.1038/355078a0. [DOI] [PubMed] [Google Scholar]
  9. Fukamachi H., Kawakami Y., Takei M., Ishizaka T., Ishizaka K., Kawakami T. Association of protein-tyrosine kinase with phospholipase C-gamma 1 in bone marrow-derived mouse mast cells. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9524–9528. doi: 10.1073/pnas.89.20.9524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fukamachi H., Yamada N., Miura T., Kato T., Ishikawa M., Gulbins E., Altman A., Kawakami Y., Kawakami T. Identification of a protein, SPY75, with repetitive helix-turn-helix motifs and an SH3 domain as a major substrate for protein tyrosine kinase(s) activated by Fc epsilon RI cross-linking. J Immunol. 1994 Jan 15;152(2):642–652. [PubMed] [Google Scholar]
  11. Furue M., Kawakami Y., Kawakami T., Katz S. I. Differential inhibition of the T cell activation pathway by dexamethasone and cyclosporine. Transplantation. 1990 Mar;49(3):560–564. doi: 10.1097/00007890-199003000-00017. [DOI] [PubMed] [Google Scholar]
  12. Gibson S., Leung B., Squire J. A., Hill M., Arima N., Goss P., Hogg D., Mills G. B. Identification, cloning, and characterization of a novel human T-cell-specific tyrosine kinase located at the hematopoietin complex on chromosome 5q. Blood. 1993 Sep 1;82(5):1561–1572. [PubMed] [Google Scholar]
  13. Gulbins E., Coggeshall K. M., Langlet C., Baier G., Bonnefoy-Berard N., Burn P., Wittinghofer A., Katzav S., Altman A. Activation of Ras in vitro and in intact fibroblasts by the Vav guanine nucleotide exchange protein. Mol Cell Biol. 1994 Feb;14(2):906–913. doi: 10.1128/mcb.14.2.906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Haslam R. J., Koide H. B., Hemmings B. A. Pleckstrin domain homology. Nature. 1993 May 27;363(6427):309–310. doi: 10.1038/363309b0. [DOI] [PubMed] [Google Scholar]
  15. Heyeck S. D., Berg L. J. Developmental regulation of a murine T-cell-specific tyrosine kinase gene, Tsk. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):669–673. doi: 10.1073/pnas.90.2.669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hunter T., Sefton B. M. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311–1315. doi: 10.1073/pnas.77.3.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hutchcroft J. E., Geahlen R. L., Deanin G. G., Oliver J. M. Fc epsilon RI-mediated tyrosine phosphorylation and activation of the 72-kDa protein-tyrosine kinase, PTK72, in RBL-2H3 rat tumor mast cells. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9107–9111. doi: 10.1073/pnas.89.19.9107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ishizaka T., Ishizaka K. Activation of mast cells for mediator release through IgE receptors. Prog Allergy. 1984;34:188–235. [PubMed] [Google Scholar]
  19. Kawakami T., Inagaki N., Takei M., Fukamachi H., Coggeshall K. M., Ishizaka K., Ishizaka T. Tyrosine phosphorylation is required for mast cell activation by Fc epsilon RI cross-linking. J Immunol. 1992 Jun 1;148(11):3513–3519. [PubMed] [Google Scholar]
  20. Kinnon C., Hinshelwood S., Levinsky R. J., Lovering R. C. X-linked agammaglobulinemia--gene cloning and future prospects. Immunol Today. 1993 Nov;14(11):554–558. doi: 10.1016/0167-5699(93)90187-P. [DOI] [PubMed] [Google Scholar]
  21. Li W., Deanin G. G., Margolis B., Schlessinger J., Oliver J. M. Fc epsilon R1-mediated tyrosine phosphorylation of multiple proteins, including phospholipase C gamma 1 and the receptor beta gamma 2 complex, in RBL-2H3 rat basophilic leukemia cells. Mol Cell Biol. 1992 Jul;12(7):3176–3182. doi: 10.1128/mcb.12.7.3176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Li W., Hu P., Skolnik E. Y., Ullrich A., Schlessinger J. The SH2 and SH3 domain-containing Nck protein is oncogenic and a common target for phosphorylation by different surface receptors. Mol Cell Biol. 1992 Dec;12(12):5824–5833. doi: 10.1128/mcb.12.12.5824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Mano H., Mano K., Tang B., Koehler M., Yi T., Gilbert D. J., Jenkins N. A., Copeland N. G., Ihle J. N. Expression of a novel form of Tec kinase in hematopoietic cells and mapping of the gene to chromosome 5 near Kit. Oncogene. 1993 Feb;8(2):417–424. [PubMed] [Google Scholar]
  24. Mayer B. J., Ren R., Clark K. L., Baltimore D. A putative modular domain present in diverse signaling proteins. Cell. 1993 May 21;73(4):629–630. doi: 10.1016/0092-8674(93)90244-k. [DOI] [PubMed] [Google Scholar]
  25. Ozawa K., Szallasi Z., Kazanietz M. G., Blumberg P. M., Mischak H., Mushinski J. F., Beaven M. A. Ca(2+)-dependent and Ca(2+)-independent isozymes of protein kinase C mediate exocytosis in antigen-stimulated rat basophilic RBL-2H3 cells. Reconstitution of secretory responses with Ca2+ and purified isozymes in washed permeabilized cells. J Biol Chem. 1993 Jan 25;268(3):1749–1756. [PubMed] [Google Scholar]
  26. Paolini R., Numerof R., Kinet J. P. Phosphorylation/dephosphorylation of high-affinity IgE receptors: a mechanism for coupling/uncoupling a large signaling complex. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10733–10737. doi: 10.1073/pnas.89.22.10733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Park D. J., Min H. K., Rhee S. G. IgE-induced tyrosine phosphorylation of phospholipase C-gamma 1 in rat basophilic leukemia cells. J Biol Chem. 1991 Dec 25;266(36):24237–24240. [PubMed] [Google Scholar]
  28. Rawlings D. J., Saffran D. C., Tsukada S., Largaespada D. A., Grimaldi J. C., Cohen L., Mohr R. N., Bazan J. F., Howard M., Copeland N. G. Mutation of unique region of Bruton's tyrosine kinase in immunodeficient XID mice. Science. 1993 Jul 16;261(5119):358–361. doi: 10.1126/science.8332901. [DOI] [PubMed] [Google Scholar]
  29. Schneider H., Cohen-Dayag A., Pecht I. Tyrosine phosphorylation of phospholipase C gamma 1 couples the Fc epsilon receptor mediated signal to mast cells secretion. Int Immunol. 1992 Apr;4(4):447–453. doi: 10.1093/intimm/4.4.447. [DOI] [PubMed] [Google Scholar]
  30. Siliciano J. D., Morrow T. A., Desiderio S. V. itk, a T-cell-specific tyrosine kinase gene inducible by interleukin 2. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11194–11198. doi: 10.1073/pnas.89.23.11194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Storrie B., Madden E. A. Isolation of subcellular organelles. Methods Enzymol. 1990;182:203–225. doi: 10.1016/0076-6879(90)82018-w. [DOI] [PubMed] [Google Scholar]
  32. Takagi M., Nakahata T., Koike K., Kobayashi T., Tsuji K., Kojima S., Hirano T., Miyajima A., Arai K., Akabane T. Stimulation of connective tissue-type mast cell proliferation by crosslinking of cell-bound IgE. J Exp Med. 1989 Jul 1;170(1):233–244. doi: 10.1084/jem.170.1.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thomas J. D., Sideras P., Smith C. I., Vorechovský I., Chapman V., Paul W. E. Colocalization of X-linked agammaglobulinemia and X-linked immunodeficiency genes. Science. 1993 Jul 16;261(5119):355–358. doi: 10.1126/science.8332900. [DOI] [PubMed] [Google Scholar]
  34. Tsukada S., Saffran D. C., Rawlings D. J., Parolini O., Allen R. C., Klisak I., Sparkes R. S., Kubagawa H., Mohandas T., Quan S. Deficient expression of a B cell cytoplasmic tyrosine kinase in human X-linked agammaglobulinemia. Cell. 1993 Jan 29;72(2):279–290. doi: 10.1016/0092-8674(93)90667-f. [DOI] [PubMed] [Google Scholar]
  35. Tsygankov A. Y., Bröker B. M., Fargnoli J., Ledbetter J. A., Bolen J. B. Activation of tyrosine kinase p60fyn following T cell antigen receptor cross-linking. J Biol Chem. 1992 Sep 15;267(26):18259–18262. [PubMed] [Google Scholar]
  36. Vetrie D., Vorechovský I., Sideras P., Holland J., Davies A., Flinter F., Hammarström L., Kinnon C., Levinsky R., Bobrow M. The gene involved in X-linked agammaglobulinaemia is a member of the src family of protein-tyrosine kinases. Nature. 1993 Jan 21;361(6409):226–233. doi: 10.1038/361226a0. [DOI] [PubMed] [Google Scholar]
  37. Yamada N., Kawakami Y., Kimura H., Fukamachi H., Baier G., Altman A., Kato T., Inagaki Y., Kawakami T. Structure and expression of novel protein-tyrosine kinases, Emb and Emt, in hematopoietic cells. Biochem Biophys Res Commun. 1993 Apr 15;192(1):231–240. doi: 10.1006/bbrc.1993.1404. [DOI] [PubMed] [Google Scholar]
  38. Yamanashi Y., Fukui Y., Wongsasant B., Kinoshita Y., Ichimori Y., Toyoshima K., Yamamoto T. Activation of Src-like protein-tyrosine kinase Lyn and its association with phosphatidylinositol 3-kinase upon B-cell antigen receptor-mediated signaling. Proc Natl Acad Sci U S A. 1992 Feb 1;89(3):1118–1122. doi: 10.1073/pnas.89.3.1118. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yu K. T., Lyall R., Jariwala N., Zilberstein A., Haimovich J. Antigen- and ionophore-induced signal transduction in rat basophilic leukemia cells involves protein tyrosine phosphorylation. J Biol Chem. 1991 Nov 25;266(33):22564–22568. [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES