PMID:9208839

Citation	Wiest, DL, Ashe, JM, Howcroft, TK, Lee, HM, Kemper, DM, Negishi, I, Singer, DS, Singer, A and Abe, R (1997) A spontaneously arising mutation in the DLAARN motif of murine ZAP-70 abrogates kinase activity and arrests thymocyte development. Immunity 6:663-71
Abstract	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 p56(lck) 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.
Links	PubMed
Keywords	Amino Acid Sequence; Animals; Base Sequence; Cell Differentiation; Immunologic Deficiency Syndromes/genetics; Lymphocyte Activation; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Molecular Sequence Data; Point Mutation; Protein-Tyrosine Kinases/genetics; Receptors, Antigen, T-Cell/physiology; Signal Transduction; T-Lymphocytes/cytology; Thymus Gland/cytology; ZAP-70 Protein-Tyrosine Kinase
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