Insulin signaling. The binding of insulin results in the cross-phosphorylation and activation of the insulin receptor. Phosphorylated sites on the receptor act as binding sites for insulin-receptor substrates such as IRS-1. The lipid kinase phosphoinositide 3-kinase binds to phosphorylated sites on IRS-1 through its regulatory domain, then converts PIP₂ into PIP₃. Binding to PIP₃ activates PIP₃-dependent protein kinase (PDK1), which phosphorylates and activates kinases such as Akt1. Activated Akt1 can then diffuse throughout the cell to continue the signal-transduction pathway.