The Insulin-like Receptor signaling pathway in Drosophila is initiated by the binding of an insulin-like peptides (ILPs) to the Insulin-like receptor (InR). ILPs are important regulators of metabolism, growth, reproduction and lifespan. Drosophila insulin-like peptides (DIPLs) bind to insulin receptors (InR), leading to receptor activation and autophosphorylation. Activated Drosophila InR (dInR) phosphorylates CHICO protein (i.e., the substrate of the insulin receptor) subsequently activates phosphoinositide-3-kinase (PI3K). Activated PI3K catalyses the conversion of PIP2 to PIP3. PIP3 acts as an intracellular second messenger and activates a cascade of protein kinases, including dPDK1 and dAkt1, resulting in phosphorylation of the transcription factor dFOXO and inhibition of its translocation into the nucleus. Inhibition of insulin/IGF signaling due to mutations in the genes encoding dInR and CHICO leads to a reduction of PI3K activity. Activity of PI3K is also reduced through activation of dPTEN phosphatase, catalyzing dephosphorylation of PIP3 to form PIP2. Decreased PIP3 leads to reduced activity of protein kinases phosphorylating dFOXO, resulting in transport of dFOXO from the cytoplasm into the nucleus. In the nucleus dFOXO activates gene expression, participating in lifespan regulation and stress resistance. The insulin/IGF signaling pathway acts in a complex regulatory network with TOR and MAPK signaling pathway involved in the regulation of numerous cellular processes, which mediate lifespan control.

Insulin References