Coordinate regulation of translation by the PI 3-kinase and mTOR pathways.
Control of translation initiation is an important means by which cells tightly regulate the critical processes of growth and proliferation. Multiple effector proteins contribute to translation initiation of specially modified mRNAs that modulate these processes. Coordinated regulation of these translational effectors by multiple signaling pathways allows the integration of information regarding mitogenic signals, energy levels, and nutrient sufficiency. The mTOR protein, in particular, serves as a sensor of all of these signals and is thought to thus serve as a crucial checkpoint control protein. Signals from the mTOR pathway converge with mitogenic inputs from the phosphoinositide (PI) 3-kinase pathway on translational effector proteins to coordinately control cellular growth, size, and cell proliferation. The translational effectors regulated by the PI 3-kinase and mTOR pathways and their roles in regulation of cellular growth will be the primary focus of this review.
Martin
Kathleen A
KA
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Blenis
John
J
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D018797:Cell Cycle Proteins; D002455:Cell Division; D048429:Cell Size; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D018816:Genes, cdc; D006801:Humans; D008115:Liver Regeneration / Q000235:genetics; D009363:Neoplasm Proteins / Q000502:physiology; D009369:Neoplasms / Q000378:metabolism / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D039561:Eukaryotic Initiation Factor-4E; D009363:Neoplasm Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D011494:Protein Kinases; D012333:RNA, Messenger; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; C087000:EIF4EBP1 protein, human; C546842:MTOR protein, human