CD95/Fas induces cleavage of the GrpL/Gads adaptor and desensitization of antigen receptor signaling
| Autor: | Thomas M. Yankee, Jonathan D. Graves, Edward A. Clark, Kevin E. Draves, Maria K. Ewings |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
T cell
B-cell receptor Receptors Antigen T-Cell Biology Jurkat cells Cell Line Mice Antigen medicine Animals Humans Cytotoxic T cell fas Receptor Antigen-presenting cell Adaptor Proteins Signal Transducing Mice Inbred BALB C Multidisciplinary NFATC Transcription Factors Caspase 3 T-cell receptor Nuclear Proteins Biological Sciences Fas receptor Molecular biology Cell biology DNA-Binding Proteins Enzyme Activation medicine.anatomical_structure Caspases Mitogen-Activated Protein Kinases Carrier Proteins Transcription Factors |
| Zdroj: | Proceedings of the National Academy of Sciences. 98:6789-6793 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.111158598 |
| Popis: | The balance between cell survival and cell death is critical for normal lymphoid development. This balance is maintained by signals through lymphocyte antigen receptors and death receptors such as CD95/Fas. In some cells, ligating the B cell antigen receptor can protect the cell from apoptosis induced by CD95. Here we report that ligation of CD95 inhibits antigen receptor-mediated signaling. Pretreating CD40-stimulated tonsillar B cells with anti-CD95 abolished B cell antigen receptor-mediated calcium mobilization. Furthermore, CD95 ligation led to the caspase-dependent inhibition of antigen receptor-induced calcium mobilization and to the activation of mitogen-activated protein kinase pathways in B and T cell lines. A target of CD95-mediated caspase 3-like activity early in the apoptotic process is the adaptor protein GrpL/Gads. GrpL constitutively interacts with SLP-76 via its C-terminal SH3 domain to regulate transcription factors such as NF-AT. Cleavage of GrpL removes the C-terminal SH3 domain so that it is no longer capable of recruiting SLP-76 to the membrane. Transfection of a truncated form of GrpL into Jurkat T cells blocked T cell antigen receptor-induced activation of NF-AT. These results suggest that CD95 signaling can desensitize antigen receptors, in part via cleavage of the GrpL adaptor. |
| Databáze: | OpenAIRE |
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