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

Alec M. Cheng, Izumi Negishi, Steven J. Anderson, Andrew C. Chan, Joseph Bolen, Dennis Y. Loh, Tony Pawson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

145 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)9797-9801
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number18
DOIs
StatePublished - Sep 2 1997

ASJC Scopus subject areas

  • General

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