Figure 2. The DAF-2/DAF-16 pathway. (A) In the presence of an agonist ligand, such as the insulin-like peptide DAF-28, the DAF-2 receptor is activated and in turn activates the phosphatidylinositol-3 OH kinase AGE-1 that catalyses the conversion of phosphatidylinositol bisphosphate (PIP2) into phosphatidylinositol trisphosphate (PIP3).On one hand, PIP3 binds to the complex AKT-1/AKT-2 and leads to the exposure of two phosphorylation sites. On the other hand, the kinase PDK-1 by binding to PiP3 is recruited to the membrane where it can phosphorylate and activate AKT-1. The kinase AKT in turn phosphorylates the transcription factor DAF-16 and thereby ensure its cytoplasmic retention. (B) In the presence of an antagonist ligand such as INS-1, (or in a
daf-2 loss of function mutant), the pathway is not active, DAF-16 is not phosphorylated and can be translocated to the nucleus where it regulates the expression of a set of stress response and antimicrobial genes.