Identification of a novel isoform of ZAP-70, truncated ZAP kinase.
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.
Department of Pathology and Immunology, Aging and Developmental Science, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Hiroyuki
H
Kuroyama
Tohru
T
Ikeda
Michiyuki
M
Kasai
Sho
S
Yamasaki
Masashi
M
Tatsumi
Masanori
M
Utsuyama
Takashi
T
Saito
Katsuiku
K
Hirokawa
D000818:Animals; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D016176:T-Lymphocyte Subsets / Q000201:enzymology; D013950:Thymus Gland / Q000166:cytology / Q000201:enzymology; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D051746:ZAP-70 Protein-Tyrosine Kinase; D018909:src Homology Domains
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D007527:Isoenzymes; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; D011948:Receptors, Antigen, T-Cell; D011994:Recombinant Proteins; D014157:Transcription Factors; D011505:Protein-Tyrosine Kinases; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C497262:Zap70 protein, mouse