A MAP4 kinase related to Ste20 is a nutrient-sensitive regulator of mTOR signalling.
The mTOR (mammalian target of rapamycin) signalling pathway is a key regulator of cell growth and is controlled by growth factors and nutrients such as amino acids. Although signalling pathways from growth factor receptors to mTOR have been elucidated, the pathways mediating signalling by nutrients are poorly characterized. Through a screen for protein kinases active in the mTOR signalling pathway in Drosophila we have identified a Ste20 family member (MAP4K3) that is required for maximal S6K (S6 kinase)/4E-BP1 [eIF4E (eukaryotic initiation factor 4E)-binding protein 1] phosphorylation and regulates cell growth. Importantly, MAP4K3 activity is regulated by amino acids, but not the growth factor insulin and is not regulated by the mTORC1 inhibitor rapamycin. Our results therefore suggest a model whereby nutrients signal to mTORC1 via activation of MAP4K3.
Findlay
Greg M
GM
Institute of Cancer Research, Cancer Research U.K. Centre of Cell and Molecular Biology, 237 Fulham Road, London SW3 6JB, U.K.
Yan
Lijun
L
Procter
Julia
J
Mieulet
Virginie
V
Lamb
Richard F
RF
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics; D039561:Eukaryotic Initiation Factor-4E / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007668:Kidney; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011494:Protein Kinases / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases; D014162:Transfection; D000077191:Wortmannin; D000099317:Hippo Kinases
D000730:Androstadienes; D029721:Drosophila Proteins; D039561:Eukaryotic Initiation Factor-4E; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D019893:Ribosomal Protein S6 Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D000077191:Wortmannin; C109163:STK24 protein, human; D000099317:Hippo Kinases; C546842:MTOR protein, human