Identification of a novel isoform of ZAP-70, truncated ZAP kinase |
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Authors: | Kuroyama Hiroyuki Ikeda Tohru Kasai Michiyuki Yamasaki Sho Tatsumi Masashi Utsuyama Masanori Saito Takashi Hirokawa Katsuiku |
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Institution: | a Department of Pathology and Immunology, Aging and Developmental Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan b Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo 162-8640, Japan c Department of Molecular Genetics, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan d Department of Veterinary Science, National Institute of Infectious Diseases, Tokyo 162-8640, Japan e Laboratory of Cell Signaling, RIKEN Center for Allergy and Immunology, Chiba 260-8670, Japan |
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Abstract: | We identified a novel cDNA encoding truncated ZAP-70, which lacked the SH2 domain and a part of interdomain B, and named it truncated ZAP kinase (TZK). TZK was expressed in the thymus, spleen, and lymph nodes with ZAP-70. TZK was expressed in CD44+CD25− thymocytes up to mature T cells, but ZAP-70 was not expressed in CD44+CD25− or CD44+CD25+ thymocytes. ZAP-70 or TZK was transfected into P116 cells derived from a Jurkat T-cell line deficient in ZAP-70. The P116 cells with ZAP-70 induced the T-cell receptor-mediated signal transduction, but the cells expressing TZK did not. While ZAP-70 was accumulated at the immune synapse, TZK was not. Meanwhile, impaired phosphorylation of SLP-76, one of the substrates of ZAP-70, in P116 cells upon pervanadate stimulation was rescued in the cells expressing TZK. These findings show that TZK is a novel isoform of ZAP-70, which is expressed in pre-T-cell receptor-minus thymocytes and functions as a kinase not associated with T-cell receptor. |
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Keywords: | ZAP-70 T lymphocyte T-cell receptor Immune synapse Microtubule-organizing center Tyrosine kinase |
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