Figure 2

TCR-induced actin-reorganization: Nck binding to phosphorylated Slp76. T cell activation is initiated by antigen-presenting cells (APCs) containing stimulatory MHC-peptide complexes. Src family protein tyrosine kinases mediate phosphorylation of TCR associated ITAMs thereby creating docking sites for the Syk-type kinase ZAP70. After activation by Src kinases, ZAP70 phosphorylates LAT. LAT contains nine tyrosine residues which, when phosphorylated, act as docking sites for adaptor proteins such as Grb2 and Gads. Slp76 is recruited to the membrane-proximal activation complex through its interaction with the SH3 domains of LAT-associated Gads. Phosphorylated Slp76 associates with the SH2 domain of Nck. Nck then recruits the multidomain adapter protein WASP. The GEF Vav, which is also recruited by Slp76, promotes the GTP-loading of the small Rho-GTPase Cdc42 that is critically involved in WASP activation. WASP then activates the Arp2/3 complex that initiates the formation of branched actin filament networks.