Crossref journal-article
Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences (341)
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.

Bibliography

Cheng, A. M., Negishi, I., Anderson, S. J., Chan, A. C., Bolen, J., Loh, D. Y., & Pawson, T. (1997). The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling. Proceedings of the National Academy of Sciences, 94(18), 9797–9801.

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)
Funders 0

None

@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} }