Requirement for Shc in TCR-mediated activation of a T cell hybridoma
| Autor: | J C, Pratt, M R, van den Brink, V E, Igras, S F, Walk, K S, Ravichandran, S J, Burakoff |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Fas Ligand Protein
Src Homology 2 Domain-Containing Transforming Protein 1 T-Lymphocytes Receptors Antigen T-Cell Apoptosis Ligands Lymphocyte Activation Transfection Cell Line src Homology Domains Mice Animals Point Mutation fas Receptor Phosphorylation Adaptor Proteins Signal Transducing GRB2 Adaptor Protein Hybridomas Membrane Glycoproteins Proteins Adaptor Proteins Vesicular Transport Shc Signaling Adaptor Proteins Receptor-CD3 Complex Antigen T-Cell Protein Biosynthesis Calcium-Calmodulin-Dependent Protein Kinases Mutation Interleukin-2 |
| Zdroj: | Journal of immunology (Baltimore, Md. : 1950). 163(5) |
| ISSN: | 0022-1767 |
| Popis: | Engagement of the TCR determines the fate of T cells to activate their functional programs, proliferate, or undergo apoptosis. The intracellular signal transduction pathways that dictate the specific outcome of receptor engagement have only been partially elucidated. The adapter protein, Shc, is involved in cytokine production, mitogenesis, transformation, and apoptosis in different cell systems. We found that Shc becomes phosphorylated on tyrosine residues upon stimulation of the TCR in DO11.10 hybridoma T cells; therefore, we investigated the role of Shc in activation-induced cell death in these cells by creating a series of stably transfected cell lines. Expression of Shc-SH2 (the SH2 domain of Shc) or Shc-Y239/240F (full-length Shc in which tyrosines 239 and 240 have been mutated to phenylalanine) resulted in the inhibition of activation-induced cell death and Fas ligand up-regulation after TCR cross-linking. Expression of wild-type Shc or Shc-Y317F had no significant effect. In addition, we found that Shc-SH2 and Shc-Y239/240F, but not Shc-Y317F, inhibited phosphorylation of extracellular signal-regulated protein kinase and production of IL-2 after TCR cross-linking. These results indicate an important role for Shc in the early signaling events that lead to activation-induced cell death and IL-2 production after TCR activation. |
| Databáze: | OpenAIRE |
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