Inhibition of PI-3-Kinase signaling by Sh3kbp1. In this figure, insulin, I, binds to its receptor, activating the receptor's tyrosine kinase activity. Insulin receptor substrates, IRS, are activated by phosphorylation. IRS phosphorylates PI-3-kinase, which migrates to the cell membrane where it generates phosphatidylinositol, PI, second messengers, which alters physiological processes. Shown here, Sh3kbp1 is capable of binding the regulatory subunit of PI-3-kinase, inhibiting its ability to generate PI second messengers, and thereby attenuating insulin signaling.