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rdf:type |
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lifeskim:mentions |
umls-concept:C0004561,
umls-concept:C0023434,
umls-concept:C0024299,
umls-concept:C0033681,
umls-concept:C0037083,
umls-concept:C0332197,
umls-concept:C1421567,
umls-concept:C1527940,
umls-concept:C1705831,
umls-concept:C1710082,
umls-concept:C1879547,
umls-concept:C2349975
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pubmed:issue |
5
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pubmed:dateCreated |
2007-2-21
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pubmed:abstractText |
Expression of ZAP-70 is an important negative prognostic factor in chronic lymphocytic leukemia (CLL). This protein tyrosine kinase is a key mediator of T-cell receptor (TCR) signaling and is structurally homologous to Syk, which plays an analogous role in B-cell receptor (BCR) signaling. Recent studies indicate that ZAP-70 may participate in BCR signaling as well, but the mechanism of action is not completely understood. We have now compared antigen receptor-induced activation of ZAP-70 in B cells and T cells by analyzing phosphorylation of critical regulatory tyrosine residues. We show that BCR-mediated activation of ZAP-70 is very inefficient in CLL and lymphoma B cells and is negligible when compared to activation of Syk. Despite the inefficient catalytic activation, the ability of ZAP-70 to recruit downstream signaling molecules in response to antigen receptor stimulation appeared relatively preserved. Moreover, ectopic expression of ZAP-70 enhanced and prolonged activation of several key mediators of BCR signaling, such as the Syk, ERK, and Akt kinases, and decreased the rate of ligand-mediated BCR internalization. We conclude that the role of ZAP-70 in BCR signaling is quite distinct from its role in TCR signaling and is likely mediated by inhibition of events that terminate the signaling response.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adaptor Proteins, Signal Transducing,
http://linkedlifedata.com/resource/pubmed/chemical/CBLB protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidylinositol 3-Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-cbl,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, B-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/SHC1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Shc Signaling Adaptor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/ZAP-70 Protein-Tyrosine Kinase,
http://linkedlifedata.com/resource/pubmed/chemical/ZAP70 protein, human
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-4971
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
109
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2032-9
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:17038529-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:17038529-Enzyme Activation,
pubmed-meshheading:17038529-Humans,
pubmed-meshheading:17038529-Leukemia, B-Cell,
pubmed-meshheading:17038529-Ligands,
pubmed-meshheading:17038529-Lymphoma, B-Cell,
pubmed-meshheading:17038529-Phosphatidylinositol 3-Kinases,
pubmed-meshheading:17038529-Phosphorylation,
pubmed-meshheading:17038529-Phosphotyrosine,
pubmed-meshheading:17038529-Protein-Tyrosine Kinases,
pubmed-meshheading:17038529-Proto-Oncogene Proteins c-cbl,
pubmed-meshheading:17038529-Receptors, Antigen, B-Cell,
pubmed-meshheading:17038529-Shc Signaling Adaptor Proteins,
pubmed-meshheading:17038529-Signal Transduction,
pubmed-meshheading:17038529-Tumor Cells, Cultured,
pubmed-meshheading:17038529-ZAP-70 Protein-Tyrosine Kinase
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pubmed:year |
2007
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pubmed:articleTitle |
ZAP-70 enhances B-cell-receptor signaling despite absent or inefficient tyrosine kinase activation in chronic lymphocytic leukemia and lymphoma B cells.
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pubmed:affiliation |
International Centre for Genetic Engineering and Biotechnology (ICGEB) Outstation-Monterotondo, Consiglio Nazionale delle Ricerche (CNR) Campus Adriano Buzzati-Traverso, Rome, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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