pubmed-article:10779765 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:10779765 | lifeskim:mentions | umls-concept:C1705831 | lld:lifeskim |
pubmed-article:10779765 | lifeskim:mentions | umls-concept:C0039194 | lld:lifeskim |
pubmed-article:10779765 | lifeskim:mentions | umls-concept:C1527940 | lld:lifeskim |
pubmed-article:10779765 | lifeskim:mentions | umls-concept:C1421567 | lld:lifeskim |
pubmed-article:10779765 | lifeskim:mentions | umls-concept:C1280500 | lld:lifeskim |
pubmed-article:10779765 | lifeskim:mentions | umls-concept:C0205160 | lld:lifeskim |
pubmed-article:10779765 | lifeskim:mentions | umls-concept:C1519063 | lld:lifeskim |
pubmed-article:10779765 | lifeskim:mentions | umls-concept:C0220905 | lld:lifeskim |
pubmed-article:10779765 | lifeskim:mentions | umls-concept:C0086597 | lld:lifeskim |
pubmed-article:10779765 | pubmed:issue | 9 | lld:pubmed |
pubmed-article:10779765 | pubmed:dateCreated | 2000-5-22 | lld:pubmed |
pubmed-article:10779765 | pubmed:abstractText | The protooncogene product Cbl has emerged as a negative regulator of tyrosine kinases. We have shown previously that Cbl binds to ZAP-70 through its N-terminal tyrosine kinase binding (TKB) domain. In this study, we demonstrate that overexpression of Cbl in Jurkat T cells decreases the TCR-induced phosphorylation of ZAP-70 and other cellular phosphoproteins. Coexpression of Cbl with ZAP-70 in COS cells reproduced the Cbl-induced reduction in the level of phosphorylated ZAP-70. The effect of Cbl was eliminated by the TKB-inactivating G306E mutation in Cbl as well as by a phenylalanine mutation of Tyr292 within the TKB domain binding site on ZAP-70. Notably, the oncogenic Cbl-70Z/3 mutant associated with ZAP-70, but did not reduce the levels of phosphorylated ZAP-70. Overexpression of Cbl, but not Cbl-G306E, in Jurkat T cells led to a decrease in the TCR-induced NF-AT luciferase reporter activity. Overexpression of the TKB domain itself, but not its G306E mutant, functioned in a dominant-negative manner and led to an increase in NF-AT reporter activity. Cbl-70Z/3-overexpressing cells exhibited an increase in both basal and TCR-induced NF-AT luciferase reporter activity, and this trend was reversed by the G306E mutation. Finally, by reconstituting a ZAP-70-deficient Jurkat T cell line, p116, we demonstrate that wild-type ZAP-70 is susceptible to the negative regulatory effect of Cbl, whereas the ZAP-70-Y292F mutant is resistant. Together, our results establish that the linker phosphorylation site Tyr292 mediates the negative regulatory effect of Cbl on ZAP-70 in T cells. | lld:pubmed |
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pubmed-article:10779765 | pubmed:language | eng | lld:pubmed |
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pubmed-article:10779765 | pubmed:citationSubset | AIM | lld:pubmed |
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pubmed-article:10779765 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:10779765 | pubmed:month | May | lld:pubmed |
pubmed-article:10779765 | pubmed:issn | 0022-1767 | lld:pubmed |
pubmed-article:10779765 | pubmed:author | pubmed-author:OtaSS | lld:pubmed |
pubmed-article:10779765 | pubmed:author | pubmed-author:RaoNN | lld:pubmed |
pubmed-article:10779765 | pubmed:author | pubmed-author:BaniGG | lld:pubmed |
pubmed-article:10779765 | pubmed:author | pubmed-author:DrukerB JBJ | lld:pubmed |
pubmed-article:10779765 | pubmed:author | pubmed-author:ReedquistK... | lld:pubmed |
pubmed-article:10779765 | pubmed:author | pubmed-author:LupherM LMLJr | lld:pubmed |
pubmed-article:10779765 | pubmed:issnType | Print | lld:pubmed |
pubmed-article:10779765 | pubmed:day | 1 | lld:pubmed |
pubmed-article:10779765 | pubmed:volume | 164 | lld:pubmed |
pubmed-article:10779765 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:10779765 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:10779765 | pubmed:pagination | 4616-26 | lld:pubmed |
pubmed-article:10779765 | pubmed:dateRevised | 2009-11-19 | lld:pubmed |
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pubmed-article:10779765 | pubmed:year | 2000 | lld:pubmed |
pubmed-article:10779765 | pubmed:articleTitle | The linker phosphorylation site Tyr292 mediates the negative regulatory effect of Cbl on ZAP-70 in T cells. | lld:pubmed |
pubmed-article:10779765 | pubmed:affiliation | Lymphocyte Biology Section, Division of Rheumatology, Immunology, and Allergy, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. | lld:pubmed |
pubmed-article:10779765 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:10779765 | pubmed:publicationType | Research Support, U.S. Gov't, P.H.S. | lld:pubmed |
pubmed-article:10779765 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
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