Figure 1.
The model of FSH/PKA/PI3K pathway. FSH induced PKA activates PP1 to dephosphorylate inhibitory sites on IRS, which facilitates phosphorylation of Tyr989 on IRS. Phosphorylated Tyr989 leads to the detachment of PI3K from GAB2 and its binding to IRS. PKA directly phosphorylates GAB2 on Ser159 and dephosphorylates p-Tyr452 through an unknown mechanism. These modifications also promote a rearrangement of the complex and the activation of PI3K. Activated PI3K converts PIP2 to PIP3, which recruits PDK, mTORC2 and Akt. PDK and mTORC2 together activate Akt. Akt then phosphorylates FoxO and keeps it out of the nucleus and thus abrogates its functions of promoting the expression of some pro-apoptotic genes, such as Bim. PKA can promote the expression of IRS through promoting the translocation of SP1, which interacts with the IRS promotor. PKA also directly phosphorylates Bad and inhibits its function.