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PMID:9275205
Citation |
Cheng, AM, Negishi, I, Anderson, SJ, Chan, AC, Bolen, J, Loh, DY and Pawson, T (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. 94:9797-801 |
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Abstract |
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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Keywords |
Animals; Antigens, CD4/immunology; Antigens, CD8/immunology; Enzyme Precursors/immunology; Intracellular Signaling Peptides and Proteins; Mice; Protein-Tyrosine Kinases/immunology; Receptors, Antigen, T-Cell, alpha-beta/genetics; Receptors, Antigen, T-Cell, alpha-beta/immunology; Signal Transduction/immunology; T-Lymphocytes/immunology; ZAP-70 Protein-Tyrosine Kinase; src Homology Domains/immunology |
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Significance
Annotations
Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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