The Caenorhabditis elegans
sgk-1 ortholog of the serum and glucocorticoid-inducible kinase SGK belongs to the AGC family of serine/threonine kinases that are activated in response to a number of extracellular stimuli. SGK-1 has a variety of physiological functions in C. elegans which include development, life span, lipid storage and stress response. SGK-1 regulates these biological processes by mechanisms that are both dependent and independent of the DAF-16/FoxO transcription factor. Here we describe a novel function for
sgk-1 in regulating DNA damage-induced germline apoptosis. We found that
sgk-1 is required to promote damage induced apoptosis by a cell non-autonomous mechanism that is also independent of
daf-16 and the canonical insulin pathway. Ablation of
sgk-1 by RNAi or mutation results in complete resistance to radiation-induced germline apoptosis. Since
sgk-1 likely functions in parallel to the canonical insulin signaling pathway, we carried out genetic epistasis analysis with components of the TORC2 pathway and found that
rict-1 functions in the same pathway as
sgk-1 to regulate DNA damage induced apoptosis in the germline. This relationship has also been observed in the regulation of lipid storage and development (Jones et al., 2009). By quantitative real time PCR we found that
egl-1 transcript is induced to normal levels in response to irradiation in both
sgk-1 and
rict-1 mutants, indicating that these genes function in parallel or downstream of
cep-1 to promote apoptosis. Since we previously showed that the insulin pathway regulates DNA damage-induced germline apoptosis through the Ras/MAPK signaling pathway (Perrin et al., 2013) we also asked if
sgk-1 also modulates Ras signaling. Ablation of
sgk-1 completely suppressed the hypersensitivity of
let-60/Ras gain-of-function mutants to damage induced apoptosis, suggesting that SGK-1 and the TORC2 pathway are important determinants of Ras signaling in the germline. We are currently investigating the levels of phosphorylated MPK-1/Erk in
sgk-1 mutants which will help us better understand the cross-talk between these pathways. Currently, we are also focusing on how
sgk-1 interacts with the core cell death components to regulate cell death.