ZAP-70 is essential for the T cell antigen receptor-induced plasma membrane targeting of SOS and Vav in T cells

Translocation of the SOS and Vav GDP/GTP exchange factors proximal to Ras a nd Pac GTPases localized in the plasma membrane glycolipid-enriched microdo mains is a pivotal step required for T cell antigen receptor-induced T cell activation. Here we demonstrate that the T cell antigen receptor xi-chain- associated ZAP-70 kinase and T cell antigen receptor xi-chain immunorecepto r tyrosine-based activation motifs are essential for the membrane recruitme nt of SOS and Vav. Plasma membrane targeting of SOS or Vav begins with the assembly of ZAP-70 with Grb-2 and SOS. The subsequent tyrosine phosphorylat ion of LAT (linker for activation of T cell) by ZAP-70 leads to a shift in equilibrium from the ZAP-70.Grb-2.SOS(Vav) complex to the (Vav)SOS.Grb-2.LA T complex. This shift results in the targeting of SOS and Vav into glycolip id-enriched microdomains and initiation of the Ras and Rac signaling cascad es involved in T cell activation, proliferation, and cytokine production.