title: Functional interaction of mammalian target of rapamycin complexes in regulating mammalian cell size and cell cycle.
abstract: Dysregulation of the mammalian target of rapamycin (mTOR) kinase pathway is centrally involved in a wide variety of cancers and human genetic diseases. In mammalian cells, mTOR is part of two different kinase complexes: mTORC1 composed of mTOR, raptor and mLST8, and mTORC2 containing mTOR, rictor, sin1 and mLST8. Whereas, mTORC1 is known to be a pivotal regulator of cell size and cell cycle control, the question whether the recently discovered mTORC2 complex is involved in these processes remains elusive. We report here that the mTORC1-mediated consequences on cell cycle and cell size are separable and do not involve effects on mTORC2 activity. However, we show that mTORC2 itself is a potent regulator of mammalian cell size and cell cycle via a mechanism involving the Akt/TSC2/Rheb cascade. Our data are of relevance for the understanding of the molecular development of the many human diseases caused by deregulation of upstream and downstream effectors of mTOR.
authors.affiliation: Medical Genetics, Medical University of Vienna, 1090 Vienna, Austria.
authors.forename: Margit
authors.initials: M
authors.lastname: Rosner
authors.forename: Christiane
authors.initials: C
authors.lastname: Fuchs
authors.forename: Nicol
authors.initials: N
authors.lastname: Siegel
authors.forename: Alessandro
authors.initials: A
authors.lastname: Valli
authors.forename: Markus
authors.initials: M
authors.lastname: Hengstschläger
mesh_terms: D002453:Cell Cycle; D002460:Cell Line; D048429:Cell Size; D006801:Humans; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases
chemical_list: D046912:Multiprotein Complexes; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases