PMID- 16631613
OWN - NLM
STAT- MEDLINE
DCOM- 20060622
LR  - 20211203
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 344
IP  - 3
DP  - 2006 Jun 9
TI  - Localization of Rheb to the endomembrane is critical for its signaling function.
PG  - 869-80
AB  - Rheb, a small GTPase, has emerged as a key molecular switch that directly 
      regulates the activity of the mammalian target of rapamycin (mTOR). Similar to 
      other members of the Ras superfamily, Rheb has a C-terminal CaaX box that is 
      subject to farnesylation. This study reports that farnesylation is a key 
      determinant of Rheb's subcellular localization and directs its association with 
      the endomembrane. Timed imaging of live cells expressing EGFP-Rheb reveals that 
      following brief association with the ER, Rheb localizes to highly ordered, 
      distinct structures within the cytoplasm that display characteristics of Golgi 
      membranes. Failure of Rheb to localize to the endomembrane impairs its ability to 
      interact with mTOR and activate downstream targets. Consistent with the notion 
      that the endomembrane may serve as a platform for the assembly of a functional 
      Rheb/mTOR complex, treatment of cells with brefeldin A interferes with 
      transmission of Rheb signals to p70S6K.
FAU - Buerger, Claudia
AU  - Buerger C
AD  - Division of Signaling Biology, Ontario Cancer Institute, University Health 
      Network, 610 University Ave, Toronto, Ont., Canada M5G 2M9.
FAU - DeVries, Ben
AU  - DeVries B
FAU - Stambolic, Vuk
AU  - Stambolic V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060419
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Neuropeptides)
RN  - 0 (RHEB protein, human)
RN  - 0 (Ras Homolog Enriched in Brain Protein)
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 3.6.5.2 (Monomeric GTP-Binding Proteins)
SB  - IM
MH  - Cell Line
MH  - Cell Membrane/*metabolism
MH  - Golgi Apparatus/*metabolism
MH  - Humans
MH  - Kidney/*metabolism
MH  - Monomeric GTP-Binding Proteins/*metabolism
MH  - Neuropeptides/*metabolism
MH  - Protein Kinases/*metabolism
MH  - Ras Homolog Enriched in Brain Protein
MH  - Signal Transduction/*physiology
MH  - Subcellular Fractions/metabolism
MH  - TOR Serine-Threonine Kinases
EDAT- 2006/04/25 09:00
MHDA- 2006/06/23 09:00
CRDT- 2006/04/25 09:00
PHST- 2006/03/23 00:00 [received]
PHST- 2006/03/29 00:00 [accepted]
PHST- 2006/04/25 09:00 [pubmed]
PHST- 2006/06/23 09:00 [medline]
PHST- 2006/04/25 09:00 [entrez]
AID - S0006-291X(06)00774-1 [pii]
AID - 10.1016/j.bbrc.2006.03.220 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2006 Jun 9;344(3):869-80. doi: 
      10.1016/j.bbrc.2006.03.220. Epub 2006 Apr 19.