The Insulin/IGF signaling (IIS) pathway is an evolutionarily conserved pathway that regulates fundamental biological processes such as development, metabolism, fecundity, cellular stress resistance and aging, in many organisms including fly and mammals. In C. elegans, IIS regulates dauer formation, longevity, fat metabolism, stress response, and innate immunity. This pathway is initiated through the Insulin-IGF receptor ortholog
daf-2, which activates a phosphorylation cascade. The ultimate outcome of the signaling pathway is the phosphorylation of the forkhead transcription factor DAF-16. Phosphorylated DAF-16 is retained in the cytoplasm, functionally inhibiting the transcription of a number of DAF-16 regulated genes.