title: TSC2: filling the GAP in the mTOR signaling pathway.
abstract: The tumor-suppressor proteins TSC1 and TSC2 are associated with an autosomal dominant disorder known as tuberous sclerosis complex (TSC). TSC1 and TSC2 function as a heterodimer to inhibit cell growth and proliferation. Another protein, mTOR (mammalian target of rapamycin), is regarded as a central controller of cell growth in response to growth factors, cellular energy and nutrient levels. Recent breakthroughs in TSC research link the TSC1/2 heterodimer protein to the mTOR signaling network. It has recently been shown that TSC2 has GTPase-activating protein (GAP) activity towards the Ras family small GTPase Rheb (Ras homolog enriched in brain), and TSC1/2 antagonizes the mTOR signaling pathway via stimulation of GTP hydrolysis of Rheb. Thus, TSC1/2 and Rheb have pivotal roles in mediating growth factors, nutrient and energy sensing signals to mTOR-dependent targets. These discoveries lend new insight into TSC pathogenesis.
authors.affiliation: Department of Biological Chemistry and Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: Michael N
authors.initials: MN
authors.lastname: Corradetti
authors.forename: Ken
authors.initials: K
authors.lastname: Inoki
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
mesh_terms: D000818:Animals; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000037:antagonists & inhibitors; D009479:Neuropeptides / Q000037:antagonists & inhibitors; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism*; D000076205:Ras Homolog Enriched in Brain Protein; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D058570:TOR Serine-Threonine Kinases; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D020690:GTPase-Activating Proteins; D009479:Neuropeptides; D047428:Protein Kinase Inhibitors; C490211:RHEB protein, human; D000076205:Ras Homolog Enriched in Brain Protein; D012097:Repressor Proteins; C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins