Fig. 3. PLC and cofilin are the gradient-sensing machinery in adenocarcinoma cells. In response to EGF stimulation, PLC becomes activated. By hydrolyzing PtdIns(4,5)P₂ (PIP2), it activates cofilin. By severing actin filaments, cofilin increases the number of free barbed ends, producing the platform for the Arp2/3 complex and Ena/VASP proteins. This allows initial protrusion and determines the direction of movement. Activation of PI3K via EGF and its signaling to Arp2/3 promotes the formation of a stable lamellipod and efficient migration (see text for details). The phosphatase SSH and 14-3-3 proteins might be involved in regulating the phosphorylation state of cofilin. Red arrows indicate enzymatic reactions. EGFR, epidermal growth factor receptor; PIP3, PtdIns(3,4,5)P₃; SSH, Slingshot.