title: The mTOR pathway and its role in human genetic diseases.
abstract: The signalling components upstream and downstream of the protein kinase mammalian target of rapamycin (mTOR) are frequently altered in a wide variety of human diseases. Upstream of mTOR key signalling molecules are the small GTPase Ras, the lipid kinase PI3K, the Akt kinase, and the GTPase Rheb, which are known to be deregulated in many human cancers. Mutations in the mTOR pathway component genes TSC1, TSC2, LKB1, PTEN, VHL, NF1 and PKD1 trigger the development of the syndromes tuberous sclerosis, Peutz-Jeghers syndrome, Cowden syndrome, Bannayan-Riley-Ruvalcaba syndrome, Lhermitte-Duclos disease, Proteus syndrome, von Hippel-Lindau disease, Neurofibromatosis type 1, and Polycystic kidney disease, respectively. In addition, the tuberous sclerosis proteins have been implicated in the development of several sporadic tumors and in the control of the cyclin-dependent kinase inhibitor p27, known to be of relevance for several cancers. Recently, it has been recognized that mTOR is regulated by TNF-alpha and Wnt, both of which have been shown to play critical roles in the development of many human neoplasias. In addition to all these human diseases, the role of mTOR in Alzheimer's disease, cardiac hypertrophy, obesity and type 2 diabetes is discussed.
authors.affiliation: Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: Margit
authors.initials: M
authors.lastname: Rosner
authors.forename: Michaela
authors.initials: M
authors.lastname: Hanneder
authors.forename: Nicol
authors.initials: N
authors.lastname: Siegel
authors.forename: Alessandro
authors.initials: A
authors.lastname: Valli
authors.forename: Christiane
authors.initials: C
authors.lastname: Fuchs
authors.forename: Markus
authors.initials: M
authors.lastname: Hengstschläger
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases
chemical_list: D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases