TSC2: filling the GAP in the mTOR signaling pathway.

Journal Article (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

International Standard Serial Number (ISSN)

  • 0968-0004

Digital Object Identifier (DOI)

  • 10.1016/j.tibs.2003.11.007


  • eng

Conference Location

  • England