Figure 8.

Model depicting the regulation of DNA damage-induced germ cell apoptosis by C. elegans PI3K pathway components. DAF-2 promotes apoptosis independently of AKT-1 by selectively engaging AKT-2 to regulate DAF-16 (AKT-1 inhibits CEP-1 from within damaged germ cells). PDK-1 functions through CED-4 and at least partially through AKT-2/DAF-16 to promote apoptosis downstream of CEP-1 and EGL-1. Although PDK-1 cannot promote apoptosis in the absence of CEP-1 and EGL-1, both DAF-2 and PDK-1 are required for amplification of LET-60/Ras signals that promote MPK-1/ERK phosphorylation and increase damage-induced apoptosis in the germline. SGK-1 promotes damage-induced germ cell apoptosis independently of the canonical Insulin/IGF-1 pathway. Arrows indicate activation, cross-hatches inhibition