Figure 1: WASp and WAVE interactions following TCR activation. A sequential orchestrated chain of events takes place within the cell following TCR engagement: LAT adaptor protein phosphorylation by ZAP70, leads to the recruitment of the SLP-76, Nck and VAV triple molecular complex. Nck recruits WASp (Right) to the TCR site, while VAV activates the Rho GTPase Cdc42. GTP-bound Cdc42 then binds WASp, releasing WASp from autoinhibition. Additional phosphorylation at tyrosine 291 by the protein tyrosine kinase (PTK) stabilizes WASp active state. Subsequently, WASp mediates Arp2/3-dependent branched actin polymerization. The molecular mechanisms of WAVE activation are poorly understood. WAVE is regulated as part of a hetero-pentameric complex that includes: PIR121 (Sra1), Hem-1 (Nap1), Abi and HSPC300. WAVE mediates Arp2/3-dependent actin polymerization. Three requirements are necessary for the recruitment and activation of the WAVE complex (Left): (1) Binding the Rho GTPase, Rac1, which can be activated by VAV (2) binding to lipid vesicles containing acidic phospholipids, i.e. PIP3 and (3) a specific mode of phosphorylation.