Abstract
An early stage in thymocyte development, after rearrangement of the β chain genes of the T cell receptor (TCR), involves expression of the pre-TCR complex and accompanying differentiation of CD4−CD8−double negative (DN) cells to CD4+CD8+double positive (DP) cells. The ZAP-70 and Syk tyrosine kinases each contain two N-terminal SH2 domains that bind phosphorylated motifs in antigen receptor subunits and are implicated in pre-T receptor signaling. However, mice deficient in either ZAP-70 or Syk have no defect in the formation of DP thymocytes. Here we show that, in mice lacking both Syk and ZAP-70, DN thymocytes undergo β chain gene rearrangement but fail to initiate clonal expansion and are incapable of differentiating into DP cells after expression of the pre-TCR. These data suggest that the ZAP-70 and Syk tyrosine kinases have crucial but overlapping functions in signaling from the pre-TCR and hence in early thymocyte development.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 10:44 a.m.) |
Deposited | 2 years, 4 months ago (April 22, 2023, 8:32 a.m.) |
Indexed | 3 months, 3 weeks ago (May 2, 2025, 8:33 a.m.) |
Issued | 27 years, 11 months ago (Sept. 2, 1997) |
Published | 27 years, 11 months ago (Sept. 2, 1997) |
Published Online | 27 years, 11 months ago (Sept. 2, 1997) |
Published Print | 27 years, 11 months ago (Sept. 2, 1997) |
@article{Cheng_1997, title={The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling}, volume={94}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.94.18.9797}, DOI={10.1073/pnas.94.18.9797}, number={18}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Cheng, Alec M. and Negishi, Izumi and Anderson, Steven J. and Chan, Andrew C. and Bolen, Joseph and Loh, Dennis Y. and Pawson, Tony}, year={1997}, month=sep, pages={9797–9801} }