title: Vav and SLP-76 interact and functionally cooperate in IL-2 gene activation.
abstract: T cell antigen receptor (TCR) stimulation induces tyrosine phosphorylation of many intracellular proteins, including the proto-oncogene Vav, which is expressed exclusively in hematopoietic and trophoblast cells. Vav is critical for lymphocyte development and activation. Overexpression of Vav in Jurkat T cells leads to potentiation of TCR-mediated IL-2 gene activation. However, the biochemical function of Vav is unknown. Here, we demonstrate that the major induced tyrosine phosphoprotein associated with Vav is the hematopoietic cell-specific SLP-76. The Vav SH2 domain is required for this interaction and for TCR-mediated Vav tyrosine phosphorylation. Similar to Vav, overexpression of SLP-76 markedly potentiates TCR-mediated NF-AT and IL-2 gene activation. Furthermore, overexpression of both Vav and SLP-76 synergistically induces basal and TCR-stimulated NF-AT activation. These results suggest that a signaling complex containing Vav and SLP-76 plays an important role in lymphocyte activation.
authors.affiliation: Department of Microbiology and Immunology, Howard Hughes Medical Institute, University of California, San Francisco 94143, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wu
authors.forename: D G
authors.initials: DG
authors.lastname: Motto
authors.forename: G A
authors.initials: GA
authors.lastname: Koretzky
authors.forename: A
authors.initials: A
authors.lastname: Weiss
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D005786:Gene Expression Regulation / Q000276:immunology*; D015972:Gene Expression Regulation, Neoplastic / Q000276:immunology; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D015458:Leukemia, T-Cell; D015513:Oncogene Proteins / Q000378:metabolism* / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism* / Q000502:physiology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000276:immunology; D000090063:Proto-Oncogene Mas; D051567:Proto-Oncogene Proteins c-vav; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007376:Interleukin-2; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D010750:Phosphoproteins; D000090063:Proto-Oncogene Mas; D051567:Proto-Oncogene Proteins c-vav; C092947:SLP-76 signal Transducing adaptor proteins; C496618:VAV1 protein, human; D011505:Protein-Tyrosine Kinases