fig1

Figure 1. PI3K/mTOR pathway and regulation of eIF4F complex. (A) PI3K and its downstream effectors AKT and mTOR are activated by many extracellular stimuli. The serine/threonine protein kinase mTOR forms, by association with several binding partners (mLST8, Raptor/Rictor, and mSIN1), 2 distinct complexes mTORC1 and mTORC2. mTORC2 activation leads to actin regulation and cytoskeleton organization, while mTORC1 allows the cap-dependent translation through the 4E-BPs phosphorylation, resulting in the dissociation of these proteins from eIF4E. PI3K pathway dysregulation results in an altered proliferation, carcinogenesis, and angiogenesis. (B) The cap-binding protein eIF4E is released by 4E-BPs as a result of its phosphorylation by mTORC1, allowing eIF4F complex formation and thus permitting translation of eIF4E-sensitive mRNAs.