mTOR pathway as a target in tissue hypertrophy.
Recent work has shown that the mTOR (mammalian target of rapamycin) pathway is an integral cell growth regulator. The mTOR pathway involves two functional complexes, TORC1 and TORC2, which have been defined by both their association with raptor or rictor, respectively, and their sensitivity to short-term rapamycin inhibition. Loss of tumor suppressors TSC1 or TSC2 leads to aberrant activation of TORC1, which has been implicated in the control of cell size. As a result, both physiologic and pathologic tissue hypertrophy are associated with TORC1 activation. Some clinical examples include skeletal and cardiac muscle hypertrophy, vascular restenosis, and compensatory nephrotic hypertrophy. Clarification of the mTOR pathway may lead to increased understanding of both the etiology and consequences of aberrant cell size regulation. This review covers some of the biochemical regulation of the mTOR pathway that may be important to the regulation of cell size, and it will present several potential clinical applications where the control of cell size may be biologically significant.
Lee
Chung-Han
CH
Life Science Institute, University of Michigan, Ann Arbor, MI 48109, USA. chunghl@umich.edu
Inoki
Ken
K
Guan
Kun-Liang
KL
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D048429:Cell Size; D006801:Humans; D006984:Hypertrophy / Q000503:physiopathology; D009132:Muscles / Q000503:physiopathology; D009369:Neoplasms / Q000503:physiopathology; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases
D000903:Antibiotics, Antineoplastic; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus