CD45 Signals outside of Lipid Rafts to Promote ERK Activation, Synaptic Raft Clustering, and IL-2 Production

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...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2005-02, Vol.174 (3), p.1479-1490
Main Authors: Zhang, Min, Moran, Miriana, Round, June, Low, Teresa A, Patel, Viresh P, Tomassian, Tamar, Hernandez, Joseph D, Miceli, M. Carrie
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - antagonists & inhibitors
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Animals
Cell Line
Cell Line, Tumor
Down-Regulation - immunology
Enzyme Activation - immunology
Extracellular Signal-Regulated MAP Kinases - metabolism
Humans
Hybridomas
Interleukin-2 - antagonists & inhibitors
Interleukin-2 - biosynthesis
Leukocyte Common Antigens - biosynthesis
Leukocyte Common Antigens - genetics
Leukocyte Common Antigens - physiology
Lymphocyte Activation - genetics
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - genetics
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - metabolism
Membrane Microdomains - enzymology
Membrane Microdomains - immunology
Membrane Microdomains - metabolism
Membrane Proteins - antagonists & inhibitors
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Phosphoproteins - antagonists & inhibitors
Phosphoproteins - genetics
Phosphoproteins - metabolism
Phosphorylation
Receptors, Antigen, T-Cell - genetics
Receptors, Antigen, T-Cell - metabolism
Receptors, Antigen, T-Cell - physiology
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
Signal Transduction - genetics
Signal Transduction - immunology
Son of Sevenless Proteins - genetics
Son of Sevenless Proteins - metabolism
src Homology Domains - genetics
T-Lymphocytes - enzymology
T-Lymphocytes - immunology
T-Lymphocytes - metabolism
Tyrosine - antagonists & inhibitors
Tyrosine - metabolism
Up-Regulation - immunology
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Summary: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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.174.3.1479