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. 2017 Aug 23;8:548. doi: 10.3389/fphar.2017.00548

Figure 1.

Figure 1

DAF-16/FOXO integrates signals from different pathways to modulate aging and longevity. Insulin-like molecules bind to DAF-2 receptor to lead to the activation of PI3P pathway composed of AGE-1/AAP-1, PDK-1 as well as AKT-1/2, which inhibits DAF-16/FOXO translocation into nucleus by phosphorylation. DAF-18/PTEN and PPTR-1/PP2A negatively regulate the IIS pathway through antagonizing AGE-1/AAP-1 and AKT kinases respectively. Additionally, JNK activity increases under oxidative stress and AMPK is activated upon high AMP/ATP ratios, and both kinases subsequently phosphorylate DAF-16 to promote its activity. Signals from germline, especially in the absence of germline, DAF-16/FOXO would be activated by KRI-1 or by mir-71 in a cell non-autonomous way. TOR pathway is partially dependent on DAF-16 in the complex of TORC1•DAF-15/Raptor together with Rag GTPases such as RAGA-1/RAGC-1, RHEB-1/Rheb, and in turn, DAF-16/FOXO could also inhibit the expression of the TORC1 coactivator daf-15/Raptor.