Vav and SLP-76 Interact and Functionally Cooperate in IL-2 Gene Activation

• Published in: Immunity (Cambridge, Mass.) Mass.), 1996-06, Vol.4 (6), p.593-602
• Main Authors: Wu, Jun, Motto, David G, Koretzky, Gary A, Weiss, Arthur
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing; Gene Expression Regulation - immunology; Gene Expression Regulation, Neoplastic - immunology; Humans; Interleukin-2 - genetics; Leukemia, T-Cell; Oncogene Proteins - metabolism; Oncogene Proteins - physiology; Phosphoproteins - metabolism; Phosphoproteins - physiology; Phosphorylation; Protein-Tyrosine Kinases - immunology; Proto-Oncogene Proteins c-vav; Signal Transduction - genetics; Signal Transduction - immunology; Transcriptional Activation; Tumor Cells, Cultured
• ISSN: 1074-7613; 1097-4180
• DOI: 10.1016/S1074-7613(00)80485-9

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.