FIG. 9.
Proposed model for translational homeostasis in response to changes in eIF4E concentration. eIF4E incorporation into an eIF4F complex is regulated by the PI 3-kinase pathway, through Akt and FRAP/mTOR, which leads to the phosphorylation of 4E-BPs and p70S6k. Forced expression of eIF4E engenders a negative feedback loop by downregulation of a component of the Akt-FRAP/mTOR pathway or by activating a phosphatase (PPase) which dephosphorylates 4E-BP1 and p70S6k. This results in the dephosphorylation of p70S6k and 4E-BP1.