Abstract
T cell receptor signaling is essential for the generation and maturation of T lymphocyte precursors. Here we identify the deubiquitinating enzyme CYLD as a positive regulator of proximal T cell receptor signaling in thymocytes. CYLD physically interacted with active Lck and promoted recruitment of active Lck to its substrate, Zap70. CYLD also removed both Lys 48- and Lys 63-linked polyubiquitin chains from Lck. Because of a cell-autonomous defect in T cell development, CYLD-deficient mice had substantially fewer mature CD4(+) and CD8(+) single-positive thymocytes and peripheral T cells.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Animals
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Crosses, Genetic
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Immunity, Innate / immunology
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Inbred DBA
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Mice, Knockout
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Receptors, Antigen, T-Cell / immunology*
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Receptors, Antigen, T-Cell / metabolism
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Signal Transduction
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Specific Pathogen-Free Organisms
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T-Lymphocytes / cytology
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T-Lymphocytes / enzymology
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T-Lymphocytes / immunology*
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Tumor Suppressor Proteins / immunology*
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Tumor Suppressor Proteins / metabolism
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Ubiquitin / immunology
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Ubiquitin / metabolism
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ZAP-70 Protein-Tyrosine Kinase / metabolism
Substances
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Receptors, Antigen, T-Cell
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Tumor Suppressor Proteins
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Ubiquitin
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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ZAP-70 Protein-Tyrosine Kinase
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Zap70 protein, mouse