1. Differential Regulation of TCR-mediated Gene Transcription by Vav Family Members
- Author
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Shaheen Zakaria, Timothy S. Gomez, Doris N. Savoy, Robert T. Abraham, Simon McAdam, Daniel D. Billadeau, and Martin R Turner
- Subjects
VAV1 ,Transcription, Genetic ,T-Lymphocytes ,T cell ,Vav ,Immunology ,Receptors, Antigen, T-Cell ,Cell Cycle Proteins ,Biology ,Jurkat cells ,Jurkat Cells ,chemistry.chemical_compound ,RNA interference ,Proto-Oncogene Proteins ,medicine ,Guanine Nucleotide Exchange Factors ,Humans ,Immunology and Allergy ,GEF ,Proto-Oncogene Proteins c-vav ,Oncogene Proteins ,Regulation of gene expression ,T-cell receptor ,Brief Definitive Report ,Tyrosine phosphorylation ,Molecular biology ,medicine.anatomical_structure ,Gene Expression Regulation ,chemistry ,SRE ,Signal transduction ,signal transduction - Abstract
Although all three Vav family members are expressed in T lymphocytes, the role that Vav3 plays in T cell activation is poorly defined. Here we show that, like Vav1, Vav3 undergoes rapid tyrosine phosphorylation after T cell receptor (TCR) cross-linkage and interacts with the adaptor molecules SLP76 and 3BP2 in a SH2-dependent manner. However, depletion of Vav1 but not Vav3 protein by RNA interference affects TCR-mediated IL-2 promoter activity. In contrast, Vav3 function is specifically required for coupling TCR stimulation to serum response element–mediated gene transcription. These data indicate that, although both Vav proteins are biochemically coupled to the TCR, they regulate distinct molecular pathways leading to defined gene transcriptional events.
- Published
- 2004
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