Regulation of T cell development by the deubiquitinating enzyme CYLD.
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.
Mesh Terms:
Animals, Crosses, Genetic, Immunity, Innate, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Receptors, Antigen, T-Cell, Signal Transduction, Specific Pathogen-Free Organisms, T-Lymphocytes, Tumor Suppressor Proteins, Ubiquitin, ZAP-70 Protein-Tyrosine Kinase
Animals, Crosses, Genetic, Immunity, Innate, Lymphocyte Specific Protein Tyrosine Kinase p56(lck), Male, Mice, Mice, Inbred C57BL, Mice, Inbred DBA, Mice, Knockout, Receptors, Antigen, T-Cell, Signal Transduction, Specific Pathogen-Free Organisms, T-Lymphocytes, Tumor Suppressor Proteins, Ubiquitin, ZAP-70 Protein-Tyrosine Kinase
Nat. Immunol.
Date: Apr. 01, 2006
PubMed ID: 16501569
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