Models for Ras GEF regulation by dominant-negative Ras mutants in C. elegans VPCs. A second Ras GEF (RasGEF2) functions in parallel to SOS. It may be constitutively wired into the Ras pathway, or it may feed in only when SOS is inactivated. RasGEF2 is selectively inhibited by SUR-5. P-loop dominant-negative Ras mutants, such as G15D, strongly inactivate SOS. In model 1, inactivation of SOS by P-loop mutants permits RasGEF2 to function in the Ras pathway. Further inactivation of SUR-5 allows RasGEF2 to promote even more Ras activation. S89F dominant-negative Ras mutants only partially inactivate SOS and fail to allow RasGEF2 to feed into the Ras pathway. Therefore, loss of SUR-5 in an S89F mutant background does not enhance Ras activation. In model 2, RasGEF2 is constitutively wired into the Ras pathway, and S89F dominant-negative Ras mutants selectively inactivate RasGEF2. Thus, in an S89F background, loss of SUR-5 still fails to promote Ras activation.