Linker for activation of T cells is displaced from lipid rafts and decreases in lupus T cells after activation via the TCR/CD3 pathway
| Autor: | Martin A. Rodriguez, Susana Brun, Nursamaa Abdoel, Ana M. Blasini, Carmen Bracho |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Adult
Adolescent T-Lymphocytes CD3 Immunology Linker for Activation of T cells chemical and pharmacologic phenomena Biology Lymphocyte Activation Article Immunological synapse Young Adult Membrane Microdomains medicine Humans Lupus Erythematosus Systemic Immunology and Allergy Phosphorylation Kinase activity Child skin and connective tissue diseases Lipid raft Systemic lupus erythematosus ZAP70 T-cell receptor Middle Aged medicine.disease Cell biology Receptor-CD3 Complex Antigen T-Cell biology.protein Signal Transduction |
| Zdroj: | Clinical Immunology. 142:243-251 |
| ISSN: | 1521-6616 |
| DOI: | 10.1016/j.clim.2011.12.010 |
| Popis: | Systemic lupus erythematosus (SLE) is characterized by abnormal signal transduction mechanisms in T lymphocytes. Linker for activation of T cells (LAT) couples TCR/CD3 activation with downstream signaling pathways. We reported diminished ERK 1/2 kinase activity in TCR/CD3 stimulated lupus T cells. In this study we evaluated the expression, phosphorylation, lipid raft and immunological synapse (IS) localization and colocalization of LAT with key signalosome molecules. We observed a diminished expression and an abnormal localization of LAT in lipid rafts and at the IS in activated lupus T cells. LAT phosphorylation, capture by GST–Grb2 fusion protein, and coupling to Grb2 and PLCγ1, was similar in healthy control and lupus T cells. Our results suggest that an abnormal localization of LAT within lipid rafts and its accelerated degradation after TCR/CD3 activation may compromise the assembly of the LAT signalosome and downstream signaling pathways required for full MAPK activation in lupus T cells. |
| Databáze: | OpenAIRE |
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