Dynamic recruitment of PAK1 to the immunological synapse is mediated by PIX independently of SLP-76 and Vav1

T cell receptor engagement activates p21-activated kinase 1 (PAK1) through a LAT - SLP- 76 - Nck - Vav- Rac - dependent pathway. A second independent pathway involving a GIT-PIX- PAK1 trimolecular complex is also activated by T cell receptor ligation. Here we show a Vav- independent pathway exists that leads to PAK1 activation. In addition, PAK1, PIX and GIT1 were recruited to the T cell - antigen-presenting cell contact site independently of SLP- 76 and Vav1. PAK1 recruitment to the T cell - antigen-presenting cell interface required interaction with PIX, which also led to optimal PLC-gamma 1 activation and T cell receptor - dependent transcriptional responses. These data indicate that a pathway involving the GIT-PIX- PAK1 complex has a crucial function in PAK1 activation by recruiting PAK1 to the immunological synapse.