A spontaneously arising mutation in the DLAARN motif of murine ZAP-70 abrogates kinase activity and arrests thymocyte development
| Autor: | Dinah S. Singer, David L. Wiest, T. Kevin Howcroft, Ryo Abe, Izumi Negishi, Jennifer M. Ashe, Debbie M Kemper, Hon-Man Lee, Alfred Singer |
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| Rok vydání: | 1997 |
| Předmět: |
T-Lymphocytes
Immunology Molecular Sequence Data Receptors Antigen T-Cell chemical and pharmacologic phenomena Protein tyrosine phosphatase Thymus Gland Lymphocyte Activation Receptor tyrosine kinase MAP2K7 chemistry.chemical_compound Mice Immunology and Allergy Animals Point Mutation Amino Acid Sequence Kinase activity ZAP-70 Protein-Tyrosine Kinase biology Base Sequence Immunologic Deficiency Syndromes hemic and immune systems Tyrosine phosphorylation Cell Differentiation Protein-Tyrosine Kinases Molecular biology Mice Mutant Strains Mice Inbred C57BL Thymocyte Infectious Diseases chemistry biology.protein Cyclin-dependent kinase 9 Proto-oncogene tyrosine-protein kinase Src Signal Transduction |
| Zdroj: | Immunity. 6(6) |
| ISSN: | 1074-7613 |
| Popis: | Development of immature CD4+CD8+ thymocytes into functionally mature CD4+ and CD8+ T cells is driven by selection events that require signals transduced through the T cell antigen receptor (TCR). Transduction of TCR signals in the thymus involves tyrosine phosphorylation of the protein tyrosine kinase ZAP-70 by p56lck and results in induction of ZAP-70 enzymatic activity. We have identified a novel, spontaneously arising point mutation within a highly conserved motif (DLAARN) in the kinase domain of murine ZAP-70 that uncouples tyrosine phosphorylation of ZAP-70 from induction of ZAP-70 kinase activity. Mice homozygous for this mutation are devoid of mature T cells because thymocyte development is arrested at the CD4+CD8+ stage of differentiation. The developmental arrest is due to the inability of CD4+CD8+ thymocytes to propagate TCR signals in the absence of ZAP-70 kinase activity despite tyrosine phosphorylation of TCR-associated ZAP-70 molecules. |
| Databáze: | OpenAIRE |
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