A novel functional interaction between Vav and PKC theta is required for TCR-induced T cell activation

Vav and PKC theta play an early and important role in the TCR/CD28-induced stimulation of MAP kinases and activation of the IL-2 gene. Vav is also ess ential for actin cytoskeleton reorganization and TCR capping. Here, we repo rt that PKC theta function was selectively required in a Vav signaling path way that mediates the TCR/CD28-induced activation of JNK and the IL-2 gene and the upregulation of CD69 expression. Vav also promoted PKC theta transl ocation from the cytosol to the membrane and cytoskeleton and induced its e nzymatic activation in a CD3/CD28-initiated pathway that was dependent on R ac and on actin cytoskeleton reorganization. These findings reveal that the Vav/Rac pathway promotes the recruitment of PKC theta to the T cell synaps e and its activation, essential processes for T cell activation and IL-2 pr oduction.