CD45 Signals outside of Lipid Rafts to Promote ERK Activation, Synaptic Raft Clustering, and IL-2 Production
| Autor: | M. Carrie Miceli, Viresh P. Patel, Tamar Tomassian, Teresa A. Low, Miriana Moran, Min Zhang, June L. Round, Joseph D. Hernandez |
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| Rok vydání: | 2005 |
| Předmět: |
MAPK/ERK pathway
Recombinant Fusion Proteins T-Lymphocytes T cell Immunology Receptors Antigen T-Cell Regulator Down-Regulation Biology Lymphocyte Activation Cell Line Immunological synapse src Homology Domains Mice Membrane Microdomains Cell Line Tumor medicine Animals Humans Immunology and Allergy Phosphorylation Extracellular Signal-Regulated MAP Kinases Lipid raft Adaptor Proteins Signal Transducing Hybridomas T-cell receptor Membrane Proteins Compartmentalization (psychology) Phosphoproteins Up-Regulation Cell biology Enzyme Activation medicine.anatomical_structure Lymphocyte Specific Protein Tyrosine Kinase p56(lck) Son of Sevenless Proteins Interleukin-2 Leukocyte Common Antigens Tyrosine lipids (amino acids peptides and proteins) Signal transduction Signal Transduction |
| Zdroj: | The Journal of Immunology. 174:1479-1490 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | CD45 is dynamically repositioned within lipid rafts and the immune synapse during T cell activation, although the molecular consequences of CD45 repositioning remain unclear. In this study we examine the role of CD45 membrane compartmentalization in regulating murine T cell activation. We find that raft-localized CD45 antagonizes IL-2 production by opposing processive TCR signals, whereas raft-excluded CD45 promotes ERK-dependent polarized synaptic lipid raft clustering and IL-2 production. We propose that these dual CD45 activities ensure that only robust TCR signals proceed, whereas signals meeting threshold requirements are potentiated. Our findings highlight membrane compartmentalization as a key regulator of CD45 function and elucidate a novel signal transduction pathway by which raft-excluded CD45 positively regulates T cell activation. |
| Databáze: | OpenAIRE |
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