Signaling to cap-dependent translation initiation. Cap-dependent translation can be controlled through activation of the PI3K-mTOR and MAPK pathways. Binding of eIF4E and eIF4G is required for eIF4F function and translation of many mRNAs; however, this can be inhibited by eIF4E-binding protein (4E-BP). mTORC1 controls the binding of 4E-BP to eIF4E through phosphorylation of 4E-BP. Furthermore, mTORC1 can control the availability of eIF4A through activation of S6K1/2, which phosphorylates PDCD4, releasing eIF4A. Mitogen-activated protein kinase-interacting kinase 1/2, which is bound by eIF4G, can also regulate translation by phosphorylating eIF4E. The PI3K-mTOR and MAPK pathways converge to phosphorylate eIF4B, a cofactor of eIF4A, leading to increased eIF4A activity.