Fig. 8. Model of Cdc42-mediated cytoskeletal signaling in carcinoma cells. Cdc42 and PI3K are both activated within the first minute of EGF stimulation in carcinoma cells, and might form a positive feedback loop. At later times, PI3K also receives input from Ras, which is required for protrusion. Activated Cdc42 is upstream of Rac, which regulates the formation of adhesive structures behind the protruding edge. Cdc42 regulation of WAVE2 and/or N-WASP is required for recruitment and activation of Arp2/3 and formation of branching actin structures. Cdc42 activation of N-WASP might also be involved in directional sensing (Nakahara et al., 2003; Yamaguchi et al., 2005), in tandem with PLC-mediated activation of cofilin (Mouneimne et al., 2004).