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Syk tyrosine kinase required for mouse viability and B-cell development

An Erratum to this article was published on 15 February 1996


THE Syk cytoplasmic protein-tyrosine kinase has two amino-terminal SH2 domains and a carboxy-terminal catalytic domain1. Syk, and its close relative ZAP-70 (ref. 2), are apparently pivotal in coupling antigen- and Fc-receptors to downstream signalling events3,4. Syk associates with activated Fc receptors5, the T cell receptor complex6 and the B-cell antigen-receptor complex (BCR) in immature and mature B lymphocytes7. On receptor activation, the tandem SH2 domains of Syk bind dual phosphotyrosine sites in the conserved ITAM motifs of receptor signalling chains, such as the immunoglobulin α and β-chains of the BCR, leading to Syk activation3,4,8. Here we have investigated Syk function in vivo by generating a mouse strain with a targeted mutation in the syk gene. Homozygous syk mutants suffered severe haemorrhaging as embryos and died perinatally, indicating that Syk has a critical role in maintaining vascular integrity or in wound healing during embryogenesis. Analysis of syk−/− lymphoid cells showed that the syk mutation impaired the differentiation of B-lineage cells, apparently by disrupting signalling from the pre-BCR complex and thereby preventing the clonal expansion, and further maturation, of pre-B cells.

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  1. 1

    Taniguchi, T. et al. J. biol. Chem. 266, 15790–15796 (1991).

    CAS  Google Scholar 

  2. 2

    Chan, A. C., Iwashima, M., Turck, C. W. & Weiss, A. Cell 71, 649–662 (1992).

    CAS  Article  Google Scholar 

  3. 3

    DeFranco, A. L. Curr. Opin. cell. Biol. 7, 163–175 (1995).

    CAS  Article  Google Scholar 

  4. 4

    Takata, M. et al. EMBO J. 13, 1341–1349 (1994).

    CAS  Article  Google Scholar 

  5. 5

    Durden, D. L. & Liu, Y. B. Blood 84, 2102–2108 (1994).

    CAS  PubMed  Google Scholar 

  6. 6

    Chan, A. C. et al. J. Immun. 152, 4758–4766 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. 7

    Hutchcroft, J. E., Harrison, M. L. & Geahlen, R. L. J. biol. Chem. 267, 8613–8619 (1992).

    CAS  PubMed  Google Scholar 

  8. 8

    Rowley, R. B., Burkhardt, A. L., Chao, H.-G., Matsueda, G. R. & Bolen, J. B. J. biol. Chem. 270, 11590–11594 (1995).

    CAS  Article  Google Scholar 

  9. 9

    Leveen, P. et al. Genes Dev. 8, 1875–1887 (1994).

    CAS  Article  Google Scholar 

  10. 10

    Soriano, P. Genes Dev. 8, 1888–1896 (1994).

    CAS  Article  Google Scholar 

  11. 11

    Taniguchi, T. et al. J. biol. Chem. 268, 2277–2279 (1993).

    CAS  PubMed  Google Scholar 

  12. 12

    Rezaul, K., Yanagi, S., Sada, K., Taniguchi, S. & Yamamura, H. Fibrosis Hemostas. 72, 937–941 (1995).

    Google Scholar 

  13. 13

    Clark, E. A., Shattil, S. J., Ginsberg, M. H., Bolen, J. & Brugge, J. S. J. biol. Chem. 269, 28859–28864 (1994).

    CAS  PubMed  Google Scholar 

  14. 14

    Sninkai, Y. et al. Cell 68, 855–867 (1992).

    Article  Google Scholar 

  15. 15

    Arpaia, E., Shahar, M., Dadi, H., Cohen, A. & Roifman, C. M. Cell 76, 947–958 (1994).

    CAS  Article  Google Scholar 

  16. 16

    Chan, A. C. et al. Science 264, 1599–1601 (1994).

    ADS  CAS  Article  Google Scholar 

  17. 17

    Hayakawa, K., Hardy, R. R., Herzenberg, L. A. & Herzenberg, L. A. J. exp. Med. 161, 1554–1568 (1985).

    CAS  Article  Google Scholar 

  18. 18

    Hardy, R. R., Carmack, C. E., Shinton, S. A., Kemp, J. D. & Hayakawa, K. J. exp. Med. 173, 1213–1225 (1991).

    CAS  Article  Google Scholar 

  19. 19

    Kitamura, D. et al. Cell 69, 823–831 (1992).

    CAS  Article  Google Scholar 

  20. 20

    Misener, V., Downey, G. P. & Jongstra, J. Int. Immun. 3, 1129–1136 (1991).

    CAS  Article  Google Scholar 

  21. 21

    Karasuyama, H., Kudo, A. & Melchers, F. J. exp. Med. 172, 969–979 (1992).

    Article  Google Scholar 

  22. 22

    Decker, D. J., Boyle, N. E., Koziol, J. & Klinman, N. R. J. Immun. 146, 350–359 (1991).

    CAS  PubMed  Google Scholar 

  23. 23

    Spanopoulou, E. et al. Genes Dev. 8, 1030–1042 (1994).

    CAS  Article  Google Scholar 

  24. 24

    Young, F. et al. Genes Dev. 8, 1043–1057 (1994).

    CAS  Article  Google Scholar 

  25. 25

    Papavasiliou, F., Misulovin, Z., Suh, H. & Nussenzweig, M. C. Science 268, 408–411 (1995).

    ADS  CAS  Article  Google Scholar 

  26. 26

    Gu, H., Kitamura, D. & Rajewsky, K. Cell 65, 47–54 (1991).

    CAS  Article  Google Scholar 

  27. 27

    Haasner, D., Rolink, A. & Melchers, F. Int. Immun. 6, 21–30 (1994).

    CAS  Article  Google Scholar 

  28. 28

    Joyner, A. L. in Gene targeting. A practical approach (IRL, Oxford, 1993).

    Google Scholar 

  29. 29

    Mallick, C. A., Dudley, E. C., Viney, J. L., Owen, M. J. & Hayday, A. C. Cell 73, 513–519 (1993).

    CAS  Article  Google Scholar 

  30. 30

    Carlsson, L., Overmo, C. & Holmberg, D. Eur. J. Immun. 22, 71–78 (1992).

    CAS  Article  Google Scholar 

  31. 31

    Chukwuocha, R. U., Hartman, A. B. & Feeney A. J. Immunogenet. 40, 76–78 (1994).

    CAS  Article  Google Scholar 

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Cheng, A., Rowley, B., Pao, W. et al. Syk tyrosine kinase required for mouse viability and B-cell development. Nature 378, 303–306 (1995).

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