Figure 2.

Coincident activation of WASP/N-WASP by PI(4,5)P2 and either small GTPases or Nck. ARP2/3 activators related to Wiskott-Aldrich syndrome protein (WASP) are multiple domain proteins that in solution are auto-inhibited due to multiple inter-domain interactions that prevent activation of Arp2/3. The small GTPases Rac1 or Cdc42 activate the nucleation activity of Apr2/3 in the presence of specific WASP family members by binding to their GBD domains. Alternatively, some WASP variants can be activated by the multiple Src homology domains in the protein NCK binding the proline-rich domain. The extent of Arp2/3 activation and the resulting rate of actin polymerization are strongly augmented by the coincident binding of PI(4,5)P2 along with either of the protein activators.