Restoration of thymocyte development and function in zap-70-/- mice by the Syk protein tyrosine kinase.
The Syk family of protein tyrosine kinases, consisting of ZAP-70 and Syk, associate with the pre- and alphabeta T cell antigen receptors (TCRs) and undergo tyrosine phosphorylation and activation following receptor engagement. Thymocyte development in zap-70-/- mice is blocked at the CD4+CD8+ TCR(lo) stage. The presence of Syk in the thymus has raised the possibility that Syk may be able to mediate TCR function. To determine if Syk can play a role in thymocyte development, we generated zap-70-/- mice expressing a human syk cDNA. Syk expression restored both thymocyte development and function. In addition, Syk function required the CD45 transmembrane protein tyrosine phosphatase. Hence, ZAP-70 and Syk can play overlapping functions and exhibit similar regulatory mechanisms in mediating alphabeta T cell development.
Gong
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Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
White
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Johnson
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R
White
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M
Negishi
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I
Thomas
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Chan
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D000818:Animals; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D004792:Enzyme Precursors / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D004848:Epithelium / Q000254:growth & development / Q000648:ultrastructure; D005260:Female; D015870:Gene Expression; D006801:Humans; D007422:Intestines / Q000254:growth & development / Q000648:ultrastructure; D047908:Intracellular Signaling Peptides and Proteins; D017493:Leukocyte Common Antigens / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000096:biosynthesis / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D000072377:Syk Kinase; D013601:T-Lymphocytes / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D013950:Thymus Gland / Q000166:cytology / Q000254:growth & development* / Q000648:ultrastructure; D019076:Transgenes; D051746:ZAP-70 Protein-Tyrosine Kinase
D018076:DNA, Complementary; D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606897:Syk protein, mouse; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C497262:Zap70 protein, mouse; D017493:Leukocyte Common Antigens