Abstract
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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References
Taniguchi, T. et al. J. biol. Chem. 266, 15790–15796 (1991).
Chan, A. C., Iwashima, M., Turck, C. W. & Weiss, A. Cell 71, 649–662 (1992).
DeFranco, A. L. Curr. Opin. cell. Biol. 7, 163–175 (1995).
Takata, M. et al. EMBO J. 13, 1341–1349 (1994).
Durden, D. L. & Liu, Y. B. Blood 84, 2102–2108 (1994).
Chan, A. C. et al. J. Immun. 152, 4758–4766 (1994).
Hutchcroft, J. E., Harrison, M. L. & Geahlen, R. L. J. biol. Chem. 267, 8613–8619 (1992).
Rowley, R. B., Burkhardt, A. L., Chao, H.-G., Matsueda, G. R. & Bolen, J. B. J. biol. Chem. 270, 11590–11594 (1995).
Leveen, P. et al. Genes Dev. 8, 1875–1887 (1994).
Soriano, P. Genes Dev. 8, 1888–1896 (1994).
Taniguchi, T. et al. J. biol. Chem. 268, 2277–2279 (1993).
Rezaul, K., Yanagi, S., Sada, K., Taniguchi, S. & Yamamura, H. Fibrosis Hemostas. 72, 937–941 (1995).
Clark, E. A., Shattil, S. J., Ginsberg, M. H., Bolen, J. & Brugge, J. S. J. biol. Chem. 269, 28859–28864 (1994).
Sninkai, Y. et al. Cell 68, 855–867 (1992).
Arpaia, E., Shahar, M., Dadi, H., Cohen, A. & Roifman, C. M. Cell 76, 947–958 (1994).
Chan, A. C. et al. Science 264, 1599–1601 (1994).
Hayakawa, K., Hardy, R. R., Herzenberg, L. A. & Herzenberg, L. A. J. exp. Med. 161, 1554–1568 (1985).
Hardy, R. R., Carmack, C. E., Shinton, S. A., Kemp, J. D. & Hayakawa, K. J. exp. Med. 173, 1213–1225 (1991).
Kitamura, D. et al. Cell 69, 823–831 (1992).
Misener, V., Downey, G. P. & Jongstra, J. Int. Immun. 3, 1129–1136 (1991).
Karasuyama, H., Kudo, A. & Melchers, F. J. exp. Med. 172, 969–979 (1992).
Decker, D. J., Boyle, N. E., Koziol, J. & Klinman, N. R. J. Immun. 146, 350–359 (1991).
Spanopoulou, E. et al. Genes Dev. 8, 1030–1042 (1994).
Young, F. et al. Genes Dev. 8, 1043–1057 (1994).
Papavasiliou, F., Misulovin, Z., Suh, H. & Nussenzweig, M. C. Science 268, 408–411 (1995).
Gu, H., Kitamura, D. & Rajewsky, K. Cell 65, 47–54 (1991).
Haasner, D., Rolink, A. & Melchers, F. Int. Immun. 6, 21–30 (1994).
Joyner, A. L. in Gene targeting. A practical approach (IRL, Oxford, 1993).
Mallick, C. A., Dudley, E. C., Viney, J. L., Owen, M. J. & Hayday, A. C. Cell 73, 513–519 (1993).
Carlsson, L., Overmo, C. & Holmberg, D. Eur. J. Immun. 22, 71–78 (1992).
Chukwuocha, R. U., Hartman, A. B. & Feeney A. J. Immunogenet. 40, 76–78 (1994).
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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). https://doi.org/10.1038/378303a0
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DOI: https://doi.org/10.1038/378303a0
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