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Figure 3


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.





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