TSC2: filling the GAP in the mTOR signaling pathway.
Published
Journal Article (Review)
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.
Full Text
Duke Authors
Cited Authors
- Li, Y; Corradetti, MN; Inoki, K; Guan, K-L
Published Date
- January 2004
Published In
Volume / Issue
- 29 / 1
Start / End Page
- 32 - 38
PubMed ID
- 14729330
Pubmed Central ID
- 14729330
International Standard Serial Number (ISSN)
- 0968-0004
Digital Object Identifier (DOI)
- 10.1016/j.tibs.2003.11.007
Language
- eng
Conference Location
- England