T-cell receptor complex is essential for Fas signal transduction.
The Fas receptor (also known as CD95 and APO-1) is a member of the tumor necrosis factor alpha-family of death receptors that mediate T-cell responses. Here, we show that Fas receptor signaling requires a functional T-cell receptor (TCR) complex. Fas receptor directly binds to and activates TCR components in a stimulus-dependent manner. Fas receptor stimulation does not activate canonical downstream TCR pathways, but instead the TCR complex is required specifically for Fas-mediated calcium release. Importantly, null mutations in Lck, ZAP70, and the TCR alpha- and beta-chains abrogate Fas signaling. Our results reveal a direct role for the TCR complex in mediating Fas-specific signaling events critical for T-cell homeostasis.
Akimzhanov
Askar M
AM
Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Wang
Xinmin
X
Sun
Jiaren
J
Boehning
Darren
D
D017209:Apoptosis; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D020013:Calcium Signaling; D002478:Cells, Cultured; D017931:DNA Primers / Q000235:genetics; D019673:Genes, T-Cell Receptor alpha; D019674:Genes, T-Cell Receptor beta; D006801:Humans; D019169:Jurkat Cells; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D051966:Phospholipase C gamma / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
D017931:DNA Primers; C491901:FAS protein, human; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019014:fas Receptor; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck); D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; D051966:Phospholipase C gamma