Feedback Circuits Monitor and Adjust Basal Lck-Dependent Events in T Cell Receptor Signaling
| Autor: | Ying Xim Tan, Arthur Weiss, Jamie R Schoenborn, Kevan M. Shokat, Cha o Zhang |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Receptors
Antigen T-Cell chemical and pharmacologic phenomena Biology Biochemistry Article Receptor tyrosine kinase CSK Tyrosine-Protein Kinase Jurkat Cells Mice Animals Humans Src family kinase Phosphorylation Molecular Biology Tyrosine-protein kinase CSK ZAP70 T-cell receptor RNA-Binding Proteins hemic and immune systems Cell Biology Protein-Tyrosine Kinases Phosphoproteins Cell biology DNA-Binding Proteins src-Family Kinases Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Cancer research biology.protein Leukocyte Common Antigens Signal transduction Tyrosine kinase Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Science Signaling. 4 |
| ISSN: | 1937-9145 1945-0877 |
| DOI: | 10.1126/scisignal.2001893 |
| Popis: | The Src family kinase Lck is crucial for the initiation of TCR signaling. The activity of Lck is tightly controlled to prevent erroneous immune activation, yet it enables rapid cellular responses over a range of sensitivities to antigens. Here, in experiments with an analog-sensitive variant of the tyrosine kinase Csk, we report that Lck in T cells is dynamically controlled by an equilibrium between Csk and the tyrosine phosphatase CD45. By rapidly inhibiting Csk, we showed that changes in this equilibrium were sufficient to activate canonical TCR signaling pathways independently of ligand binding to the TCR. The activated signaling pathways showed sustained and enhanced phosphorylation compared to that in TCR-stimulated cells, revealing a feedback circuit that was sensitive to the basal signaling machinery. We identified the inhibitory adaptor molecule Dok-1 (downstream of kinase 1) as a candidate that may respond to alterations in basal signaling activity. Our results also suggest a role for Csk in the termination or dampening of TCR signals. |
| Databáze: | OpenAIRE |
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