Fig. 3.

WASp recruitment and activation at the immunological synapse. TCR engagement initiates a signalling cascade involving the kinases ZAP-70 and Lck, which are involved in the phosphorylation of the adaptor molecule Slp-76. Phosphorylated Slp-76 interacts with WASp via Nck and recruits the GTPase Vav-1, which mediates activation of the Rho-GTPase Cdc42 and subsequently activates WASp. Another mechanism of WASp activation is proposed to be independent of Cdc42. The Fyn kinase binds to the polyproline domain (PPP) of WASp and phosphorylates tyrosine 291 to activate WASp. Regulation of this mechanism may be through dephosphorylation by PTP-PEST, which is recruited to the synapse by CD2. See text for references.