Abstract
Crosslinking of Fas (APO-1/CD95) on the surface of T cells initiates a biochemical cascade leading to programmed cell death. We have previously shown that crosslinking of Fas with an apoptosis-inducing IgM anti-Fas mAb results in suppression of the CD3-initiated cell signaling including Ca2+ mobilization and protein tyrosine phosphorylation. We conducted experiments to decipher the mechanisms whereby the cross talk between the Fas- and CD3 signaling pathways occur. We used lysates from Jurkat T and examined the composition of the TCR ζ chain-precipitated immune complexes using immunoblots. While crosslinking of Fas affected the association of p59fyn and p56lck tyrosine kinases with the TCR ζ chain to a limited degree, it dramatically inhibited the association of the protein tyrosine kinase ZAP70 with the ζ chain. In cells that were preincubated with an apoptosis-inducing anti-Fas mAb, the binding of the protein tyrosine phosphatases SHP-1 to the TCR ζ chain was increased. These experiments indicate that crosslinking of Fas interferes with early T cell signaling events by promoting the recruitment of SHP-1 and decreasing the association of protein tyrosine kinases with TCR ζ chain. Therefore, crosslinking of Fas antigen may regulate the antigen-induced T cell response and play an active role in the T cell anergy.
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Kovacs, B., Liossis, SN.C., Gist, I.D. et al. Crosslinking of Fas/CD95 suppresses the CD3-mediated signaling events in Jurkat T cells by inhibiting the association of the T-cell receptor ζ chain with src-protein tyrosine kinases and ZAP70. Apoptosis 4, 327–334 (1999). https://doi.org/10.1023/A:1009691120129
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DOI: https://doi.org/10.1023/A:1009691120129