Figure 5. Model for WAVE2 function.

Counterclockwise from top right, the WAVE2 complex is intrinsically inactive, and must be phosphorylated before it can be activated. However, phosphorylation by itself does not activate the complex. Phosphorylated WAVE2 complex can bind acidic phospholipids, including PIP₃, or prenylated Rac-GTP, but binding to either is not sufficient for activation. Binding to both acidic phospholipids and prenylated Rac-GTP activates the WAVE2 complex, most likely though allosteric changes, leading to Arp2/3 dependent actin polymerization. Although PIP₃ is most potent, other acidic phospholipids can also activate the complex together with prenylated Rac-GTP. Cooperative association of multiple complexes on the membrane results in greatly enhanced actin nucleation. Key is at the top left corner of the diagram.