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. 1994 Oct 25;91(22):10606–10609. doi: 10.1073/pnas.91.22.10606

Bruton tyrosine kinase is tyrosine phosphorylated and activated in pre-B lymphocytes and receptor-ligated B cells.

Y Aoki 1, K J Isselbacher 1, S Pillai 1
PMCID: PMC45070  PMID: 7524098

Abstract

The gene encoding Bruton tyrosine kinase (Btk) is known to be mutated in human X chromosome-linked agammaglobulinemia and in the Xid mouse. This kinase was examined in B lymphocytes before and after antigen receptor ligation and also in pre-B cells. Btk was found to be catalytically activated and tyrosine phosphorylated in response to anti-IgM stimulation in B cells. This kinase is also constitutively phosphorylated on tyrosine residues in pre-B cells. These findings point to a functional role for Btk in pre-antigen and antigen receptor signaling during B-cell development and provide a biochemical explanation for the X-linked genetic syndromes already linked to this kinase.

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Selected References

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

  1. Anderson S. J., Levin S. D., Perlmutter R. M. Protein tyrosine kinase p56lck controls allelic exclusion of T-cell receptor beta-chain genes. Nature. 1993 Oct 7;365(6446):552–554. doi: 10.1038/365552a0. [DOI] [PubMed] [Google Scholar]
  2. Aoki Y., Isselbacher K. J., Cherayil B. J., Pillai S. Tyrosine phosphorylation of Blk and Fyn Src homology 2 domain-binding proteins occurs in response to antigen-receptor ligation in B cells and constitutively in pre-B cells. Proc Natl Acad Sci U S A. 1994 May 10;91(10):4204–4208. doi: 10.1073/pnas.91.10.4204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buckley R. H. Assessing inheritance of agammaglobulinemia. N Engl J Med. 1994 May 26;330(21):1526–1528. doi: 10.1056/NEJM199405263302111. [DOI] [PubMed] [Google Scholar]
  4. Burkhardt A. L., Brunswick M., Bolen J. B., Mond J. J. Anti-immunoglobulin stimulation of B lymphocytes activates src-related protein-tyrosine kinases. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7410–7414. doi: 10.1073/pnas.88.16.7410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cambier J. C., Bedzyk W., Campbell K., Chien N., Friedrich J., Harwood A., Jensen W., Pleiman C., Clark M. R. The B-cell antigen receptor: structure and function of primary, secondary, tertiary and quaternary components. Immunol Rev. 1993 Apr;132:85–106. doi: 10.1111/j.1600-065x.1993.tb00838.x. [DOI] [PubMed] [Google Scholar]
  6. Campbell M. A., Sefton B. M. Association between B-lymphocyte membrane immunoglobulin and multiple members of the Src family of protein tyrosine kinases. Mol Cell Biol. 1992 May;12(5):2315–2321. doi: 10.1128/mcb.12.5.2315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cherayil B. J., Pillai S. The omega/lambda 5 surrogate immunoglobulin light chain is expressed on the surface of transitional B lymphocytes in murine bone marrow. J Exp Med. 1991 Jan 1;173(1):111–116. doi: 10.1084/jem.173.1.111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dudley E. C., Petrie H. T., Shah L. M., Owen M. J., Hayday A. C. T cell receptor beta chain gene rearrangement and selection during thymocyte development in adult mice. Immunity. 1994 May;1(2):83–93. doi: 10.1016/1074-7613(94)90102-3. [DOI] [PubMed] [Google Scholar]
  9. Dymecki S. M., Niederhuber J. E., Desiderio S. V. Specific expression of a tyrosine kinase gene, blk, in B lymphoid cells. Science. 1990 Jan 19;247(4940):332–336. doi: 10.1126/science.2404338. [DOI] [PubMed] [Google Scholar]
  10. Ehlich A., Schaal S., Gu H., Kitamura D., Müller W., Rajewsky K. Immunoglobulin heavy and light chain genes rearrange independently at early stages of B cell development. Cell. 1993 Mar 12;72(5):695–704. doi: 10.1016/0092-8674(93)90398-a. [DOI] [PubMed] [Google Scholar]
  11. Gold M. R., Law D. A., DeFranco A. L. Stimulation of protein tyrosine phosphorylation by the B-lymphocyte antigen receptor. Nature. 1990 Jun 28;345(6278):810–813. doi: 10.1038/345810a0. [DOI] [PubMed] [Google Scholar]
  12. Gregory R. J., Kammermeyer K. L., Vincent W. S., 3rd, Wadsworth S. G. Primary sequence and developmental expression of a novel Drosophila melanogaster src gene. Mol Cell Biol. 1987 Jun;7(6):2119–2127. doi: 10.1128/mcb.7.6.2119. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Groettrup M., Ungewiss K., Azogui O., Palacios R., Owen M. J., Hayday A. C., von Boehmer H. A novel disulfide-linked heterodimer on pre-T cells consists of the T cell receptor beta chain and a 33 kd glycoprotein. Cell. 1993 Oct 22;75(2):283–294. doi: 10.1016/0092-8674(93)80070-u. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Hutchcroft J. E., Harrison M. L., Geahlen R. L. Association of the 72-kDa protein-tyrosine kinase PTK72 with the B cell antigen receptor. J Biol Chem. 1992 Apr 25;267(12):8613–8619. [PubMed] [Google Scholar]
  16. Karasuyama H., Kudo A., Melchers F. The proteins encoded by the VpreB and lambda 5 pre-B cell-specific genes can associate with each other and with mu heavy chain. J Exp Med. 1990 Sep 1;172(3):969–972. doi: 10.1084/jem.172.3.969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Law C. L., Sidorenko S. P., Chandran K. A., Draves K. E., Chan A. C., Weiss A., Edelhoff S., Disteche C. M., Clark E. A. Molecular cloning of human Syk. A B cell protein-tyrosine kinase associated with the surface immunoglobulin M-B cell receptor complex. J Biol Chem. 1994 Apr 22;269(16):12310–12319. [PubMed] [Google Scholar]
  18. Law D. A., Chan V. W., Datta S. K., DeFranco A. L. B-cell antigen receptor motifs have redundant signalling capabilities and bind the tyrosine kinases PTK72, Lyn and Fyn. Curr Biol. 1993 Oct 1;3(10):645–657. doi: 10.1016/0960-9822(93)90062-s. [DOI] [PubMed] [Google Scholar]
  19. Lin W. C., Desiderio S. Regulation of V(D)J recombination activator protein RAG-2 by phosphorylation. Science. 1993 May 14;260(5110):953–959. doi: 10.1126/science.8493533. [DOI] [PubMed] [Google Scholar]
  20. Lindsberg M. L., Brunswick M., Yamada H., Lees A., Inman J., June C. H., Mond J. J. Biochemical analysis of the immune B cell defect in xid mice. J Immunol. 1991 Dec 1;147(11):3774–3779. [PubMed] [Google Scholar]
  21. Malek S. N., Desiderio S. SH2 domains of the protein-tyrosine kinases Blk, Lyn, and Fyn(T) bind distinct sets of phosphoproteins from B lymphocytes. J Biol Chem. 1993 Oct 25;268(30):22557–22565. [PubMed] [Google Scholar]
  22. Mano H., Ishikawa F., Nishida J., Hirai H., Takaku F. A novel protein-tyrosine kinase, tec, is preferentially expressed in liver. Oncogene. 1990 Dec;5(12):1781–1786. [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. Pillai S., Baltimore D. Formation of disulphide-linked mu 2 omega 2 tetramers in pre-B cells by the 18K omega-immunoglobulin light chain. Nature. 1987 Sep 10;329(6135):172–174. doi: 10.1038/329172a0. [DOI] [PubMed] [Google Scholar]
  25. Pillai S., Baltimore D. The omega and iota surrogate immunoglobulin light chains. Curr Top Microbiol Immunol. 1988;137:136–139. doi: 10.1007/978-3-642-50059-6_20. [DOI] [PubMed] [Google Scholar]
  26. Pillai S. Immunoglobulin transport in B cell development. Int Rev Cytol. 1991;130:1–36. doi: 10.1016/s0074-7696(08)61500-4. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. Reth M. Antigen receptors on B lymphocytes. Annu Rev Immunol. 1992;10:97–121. doi: 10.1146/annurev.iy.10.040192.000525. [DOI] [PubMed] [Google Scholar]
  29. Saffran D. C., Parolini O., Fitch-Hilgenberg M. E., Rawlings D. J., Afar D. E., Witte O. N., Conley M. E. Brief report: a point mutation in the SH2 domain of Bruton's tyrosine kinase in atypical X-linked agammaglobulinemia. N Engl J Med. 1994 May 26;330(21):1488–1491. doi: 10.1056/NEJM199405263302104. [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. 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]
  32. Tsubata T., Reth M. The products of pre-B cell-specific genes (lambda 5 and VpreB) and the immunoglobulin mu chain form a complex that is transported onto the cell surface. J Exp Med. 1990 Sep 1;172(3):973–976. doi: 10.1084/jem.172.3.973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. 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]
  34. 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]
  35. Yamanashi Y., Kakiuchi T., Mizuguchi J., Yamamoto T., Toyoshima K. Association of B cell antigen receptor with protein tyrosine kinase Lyn. Science. 1991 Jan 11;251(4990):192–194. doi: 10.1126/science.1702903. [DOI] [PubMed] [Google Scholar]

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