Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Activity of TSC2 is inhibited by AKT-mediated phosphorylation and membrane partitioning.

http://www.ncbi.nlm.nih.gov/pubmed/16636147

Loss of tuberin, the product of TSC2 gene, increases mammalian target of rapamycin (mTOR) signaling, promoting cell growth and tumor development. However, in cells expressing tuberin, it is not known how repression of mTOR signaling is relieved to activate this pathway in response to growth factors and how hamartin participates in this process. We show that hamartin colocalizes with hypophosphorylated tuberin at the membrane, where tuberin exerts its GTPase-activating protein (GAP) activity to repress Rheb signaling. In response to growth signals, tuberin is phosphorylated by AKT and translocates to the cytosol, relieving Rheb repression. Phosphorylation of tuberin at serines 939 and 981 does not alter its intrinsic GAP activity toward Rheb but partitions tuberin to the cytosol, where it is bound by 14-3-3 proteins. Thus, tuberin bound by 14-3-3 in response to AKT phosphorylation is sequestered away from its membrane-bound activation partner (hamartin) and its target GTPase (Rheb) to relieve the growth inhibitory effects of this tumor suppressor.

Pubmed ID: 16636147 RIS Download

Mesh terms: Cell Line | Cell Membrane | Growth Substances | HeLa Cells | Humans | Microscopy, Confocal | Models, Biological | Phosphorylation | Proto-Oncogene Proteins c-akt | Tumor Suppressor Proteins | ras Proteins

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NCI NIH HHS, Id: CA16672
  • Agency: NCI NIH HHS, Id: CA63613
  • Agency: NIEHS NIH HHS, Id: ES07784
  • Agency: NIEHS NIH HHS, Id: ES08263-06S1
  • Agency: NICHD NIH HHS, Id: HD46282

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.