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Publication : The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling.

First Author  Cheng AM Year  1997
Journal  Proc Natl Acad Sci U S A Volume  94
Issue  18 Pages  9797-801
PubMed ID  9275205 Mgi Jnum  J:42818
Mgi Id  MGI:1096306 Doi  10.1073/pnas.94.18.9797
Citation  Cheng AM, et al. (1997) The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling. Proc Natl Acad Sci U S A 94(18):9797-801
abstractText  An early stage in thymocyte development, after rearrangement of the beta 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 beta 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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