FIGURE 8.

Proposed model for the role of p120RasGAP in netrin-1/DCC-mediated axon outgrowth and guidance. In the absence of netrin-1, the GAP domain of p120RasGAP maintains Ras inactive (Ras-GDP). In response to netrin-1 stimulation, DCC- Tyr(P)-1418/Tyr-1361, FAK (Tyr(P)-397), pERK, and tyrosine-phosphorylated p120RasGAP associate in a multiprotein signaling complex. Through these interactions, mediated by the N-terminal SH2-SH3-SH2 domains (NT) of p120RasGAP, Ras-GTP is released to induce sustained ERK activation in response to netrin-1, leading to axon outgrowth and growth cone attraction.