PMID- 16728407
OWN - NLM
STAT- MEDLINE
DCOM- 20060919
LR  - 20220309
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 29
DP  - 2006 Jul 21
TI  - Hyperactivation of mammalian target of rapamycin (mTOR) signaling by a 
      gain-of-function mutant of the Rheb GTPase.
PG  - 19793-7
AB  - Gain-of-function mutants of Ras and Rho family small GTPases have proven to be 
      important tools in analyzing signaling downstream of these small GTPases. The 
      Ras-related GTPase Rheb has emerged as a key player downstream of TSC1-2 in 
      activating signaling to mammalian target of rapamycin (mTOR) effectors of cell 
      growth such as S6K and 4E-BP1. The TSC1-2 tumor suppressor complex has been shown 
      to act as a RhebGAP, converting Rheb from a GTP-bound to a GDP-bound form. Here 
      we report the identification of a mutant Rheb (S16HRheb) that exhibits 
      gain-of-function properties. At endogenous levels of expression S16HRheb exhibits 
      increased GTP loading in vivo and is resistant to TSC1-2 GAP in vitro. Compared 
      with wild-type Rheb, S16HRheb is more active at promoting the phosphorylation of 
      the mTOR effectors S6K1 and 4E-BP1. Thus S16HRheb will help to identify proximal 
      signaling events downstream of Rheb and allow potential Rheb-independent 
      functions downstream of TSC1-2 to be investigated.
FAU - Yan, Lijun
AU  - Yan L
AD  - Institute of Cancer Research, Cancer Research UK Centre of Cell and Molecular 
      Biology, London SW7 6JB, UK.
FAU - Findlay, Greg M
AU  - Findlay GM
FAU - Jones, Rebecca
AU  - Jones R
FAU - Procter, Julia
AU  - Procter J
FAU - Cao, Yunhong
AU  - Cao Y
FAU - Lamb, Richard F
AU  - Lamb RF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060525
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Neuropeptides)
RN  - 0 (RHEB protein, human)
RN  - 0 (Ras Homolog Enriched in Brain Protein)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.1.- (GTP Phosphohydrolases)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Conserved Sequence
MH  - Enzyme Activation
MH  - GTP Phosphohydrolases/metabolism
MH  - Guanosine Triphosphate/metabolism
MH  - Humans
MH  - Kidney
MH  - Molecular Sequence Data
MH  - Monomeric GTP-Binding Proteins/chemistry/genetics
MH  - Mutation
MH  - Neuropeptides/chemistry/genetics
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Kinases/*metabolism
MH  - Ras Homolog Enriched in Brain Protein
MH  - Sequence Alignment
MH  - Sequence Homology, Amino Acid
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - rho GTP-Binding Proteins/*genetics/*metabolism
EDAT- 2006/05/27 09:00
MHDA- 2006/09/20 09:00
CRDT- 2006/05/27 09:00
PHST- 2006/05/27 09:00 [pubmed]
PHST- 2006/09/20 09:00 [medline]
PHST- 2006/05/27 09:00 [entrez]
AID - S0021-9258(19)76292-9 [pii]
AID - 10.1074/jbc.C600028200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Jul 21;281(29):19793-7. doi: 10.1074/jbc.C600028200. Epub 2006 
      May 25.