| First Author | Kong YY | Year | 1998 |
| Journal | J Exp Med | Volume | 188 |
| Issue | 11 | Pages | 2099-111 |
| PubMed ID | 9841924 | Mgi Jnum | J:79537 |
| Mgi Id | MGI:2388450 | Doi | 10.1084/jem.188.11.2099 |
| Citation | Kong YY, et al. (1998) Vav regulates peptide-specific apoptosis in thymocytes. J Exp Med 188(11):2099-111 |
| abstractText | The protooncogene Vav functions as a GDP/GTP exchange factor (GEF) for Rho-like small GTPases involved in cytoskeletal reorganization and cytokine production in T cells. Gene-targeted mice lacking Vav have a severe defect in positive and negative selection of T cell antigen receptor transgenic thymocytes in vivo, and vav-/- thymocytes are completely resistant to peptide-specific and anti-CD3/anti-CD28-mediated apoptosis. Vav acts upstream of mitochondrial pore opening and caspase activation. Biochemically, Vav regulates peptide-specific Ca2+ mobilization and actin polymerization. Peptide-specific cell death was blocked both by cytochalasin D inhibition of actin polymerization and by inhibition of protein kinase C (PKC). Activation of PKC with phorbol ester restored peptide-specific apoptosis in vav-/- thymocytes. Vav was found to bind constitutively to PKC-theta in thymocytes. Our results indicate that peptide-triggered thymocyte apoptosis is mediated via Vav activation, changes in the actin cytoskeleton, and subsequent activation of a PKC isoform. |
