Fig. 6.

Proposed mechanism of N-WASP activation by Nck. In the autoinhibited conformation, the N-WASP C helix binds intramolecularly to the GBD. Nck binds to tyrosine-phosphorylated receptors on the membrane and activates N-WASP by competitively displacing the C helix from the GBD with its inter-SH3AB linker. The released VCA segment is available to activate the Arp2/3 complex. Polyvalent interactions between the SH3 domains of Nck and the proline-rich region (PRR) of N-WASP can lead to higher-order oligomer formation, increasing the local density of activated N-WASP molecules.