PMID- 12773158
OWN - NLM
STAT- MEDLINE
DCOM- 20040323
LR  - 20211203
IS  - 0300-5127 (Print)
IS  - 0300-5127 (Linking)
VI  - 31
IP  - Pt 3
DP  - 2003 Jun
TI  - United at last: the tuberous sclerosis complex gene products connect the 
      phosphoinositide 3-kinase/Akt pathway to mammalian target of rapamycin (mTOR) 
      signalling.
PG  - 573-8
AB  - The molecular interplay between the phosphoinositide 3-kinase (PI3K) pathway and 
      mammalian target of rapamycin (mTOR) signalling in the control of cell growth and 
      proliferation has been the subject of much interest and debate amongst cell 
      biologists. A recent escalation of research in this area has come from the 
      discovery of the tuberous sclerosis complex gene products, tuberin and hamartin, 
      as central regulators of mTOR activation. The PI3K effector Akt/protein kinase B 
      has been found to directly phosphorylate tuberin and is thereby thought to 
      activate mTOR through inhibition of the tuberin-hamartin complex. The many recent 
      studies aimed at defining the molecular nature of this revamped PI3K/Akt/mTOR 
      pathway are reviewed here. The collective data discussed have laid the groundwork 
      for important new insights into the many cancers caused by aberrant PI3K 
      activation and the clinically challenging tuberous sclerosis complex disease and 
      have suggested a possible means of treatment for both.
FAU - Manning, B D
AU  - Manning BD
AD  - Department of Cell Biology, Harvard Medical School, Division of Signal 
      Transduction, Beth Israel Deaconess Medical Center, 4 Blackfan Circle, Boston, MA 
      02115, USA.
FAU - Cantley, L C
AU  - Cantley LC
LA  - eng
GR  - R01 GM041890/GM/NIGMS NIH HHS/United States
GR  - GM41890/GM/NIGMS NIH HHS/United States
GR  - GM56203/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - England
TA  - Biochem Soc Trans
JT  - Biochemical Society transactions
JID - 7506897
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Repressor Proteins)
RN  - 0 (TSC1 protein, human)
RN  - 0 (TSC2 protein, human)
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 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.11.1 (AKT1 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 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Genes, Tumor Suppressor
MH  - Humans
MH  - Phosphatidylinositol 3-Kinases/*genetics
MH  - Protein Kinases/*genetics/physiology
MH  - *Protein Serine-Threonine Kinases
MH  - Protein-Tyrosine Kinases/genetics
MH  - Proteins/genetics
MH  - Proto-Oncogene Proteins/genetics
MH  - Proto-Oncogene Proteins c-akt
MH  - Repressor Proteins/genetics
MH  - Signal Transduction/genetics
MH  - TOR Serine-Threonine Kinases
MH  - Tuberous Sclerosis/enzymology/*genetics
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins
RF  - 49
EDAT- 2003/05/30 05:00
MHDA- 2004/03/24 05:00
CRDT- 2003/05/30 05:00
PHST- 2003/05/30 05:00 [pubmed]
PHST- 2004/03/24 05:00 [medline]
PHST- 2003/05/30 05:00 [entrez]
AID - 10.1042/bst0310573 [doi]
PST - ppublish
SO  - Biochem Soc Trans. 2003 Jun;31(Pt 3):573-8. doi: 10.1042/bst0310573.