PMID- 16391386
OWN - NLM
STAT- MEDLINE
DCOM- 20060217
LR  - 20220225
IS  - 1535-1084 (Print)
IS  - 1535-1084 (Linking)
VI  - 7
IP  - 4
DP  - 2005
TI  - Positive and negative regulation of TSC2 activity and its effects on downstream 
      effectors of the mTOR pathway.
PG  - 287-96
AB  - Tuberous sclerosis is an autosomal-dominant disorder caused by the mutation of 
      one of the two tumor suppressor genes: TSC1 or TSC2, encoding protein products, 
      hamartin, and tuberin, respectively. Both proteins form intracellular complexes 
      exerting inhibitory activity on mammalian target of rapamycin (mTOR) kinase. It 
      has been demonstrated that signal transduction from tuberin to mTOR is mediated 
      by a G protein, Ras homologue enriched in brain (Rheb). In normal cells, tuberin 
      having GTPase-activating protein properties toward Rheb controls signals of 
      nutrient depletion, hypoxia, or stress, not allowing activation of mTOR and 
      subsequent protein translation and cell proliferation. However, when 
      environmental conditions change, tuberin is phosphorylated and it forms a complex 
      with hamartin is degraded, and downstream targets of mTOR, S6K, and eEF2K, can be 
      activated. In this review, we summarize very recent information contributing to 
      our knowledge of TSC2 regulation by four cellular signaling pathways: PI3K/Akt, 
      Ras/MAPK, LKB1/AMPK, and REDD1.
FAU - Jozwiak, Jaroslaw
AU  - Jozwiak J
AD  - Department of Histology and Embryology, Center for Biostructure Research, Medical 
      University of Warsaw, 02-004 Warsaw, ul. Chalubinskiego 5, Poland. 
      jjozwiak@atdv.com.pl
FAU - Jozwiak, Sergiusz
AU  - Jozwiak S
FAU - Grzela, Tomasz
AU  - Grzela T
FAU - Lazarczyk, Maciej
AU  - Lazarczyk M
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United States
TA  - Neuromolecular Med
JT  - Neuromolecular medicine
JID - 101135365
RN  - 0 (DDIT4 protein, human)
RN  - 0 (TSC1 protein, human)
RN  - 0 (TSC2 protein, human)
RN  - 0 (Transcription Factors)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (STK11 protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - AMP-Activated Protein Kinase Kinases
MH  - Animals
MH  - Humans
MH  - MAP Kinase Signaling System/physiology
MH  - Phosphatidylinositol 3-Kinases/physiology
MH  - Protein Biosynthesis
MH  - Protein Kinases/*physiology
MH  - Protein Serine-Threonine Kinases/physiology
MH  - Proto-Oncogene Proteins c-akt/physiology
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factors/metabolism
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/*metabolism/physiology
MH  - ras Proteins/physiology
RF  - 54
EDAT- 2006/01/05 09:00
MHDA- 2006/02/18 09:00
CRDT- 2006/01/05 09:00
PHST- 2005/06/06 00:00 [received]
PHST- 2005/06/28 00:00 [revised]
PHST- 2005/06/29 00:00 [accepted]
PHST- 2006/01/05 09:00 [pubmed]
PHST- 2006/02/18 09:00 [medline]
PHST- 2006/01/05 09:00 [entrez]
AID - NMM:7:4:287 [pii]
AID - 10.1385/NMM:7:4:287 [doi]
PST - ppublish
SO  - Neuromolecular Med. 2005;7(4):287-96. doi: 10.1385/NMM:7:4:287.