The Syk and ZAP-70 SH2-containing tyrosine kinases are implicated in pre-T cell receptor signaling.
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.
Cheng
A M
AM
Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, Ontario, M5G 1X5, Canada.
Negishi
I
I
Anderson
S J
SJ
Chan
A C
AC
Bolen
J
J
Loh
D Y
DY
Pawson
T
T
D000818:Animals; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D004792:Enzyme Precursors / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000276:immunology*; D051746:ZAP-70 Protein-Tyrosine Kinase; D018909:src Homology Domains / Q000276:immunology
D015704:CD4 Antigens; D016827:CD8 Antigens; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D051746:ZAP-70 Protein-Tyrosine Kinase; C497262:Zap70 protein, mouse