PMID- 15809346
OWN - NLM
STAT- MEDLINE
DCOM- 20050825
LR  - 20211203
IS  - 0021-924X (Print)
IS  - 0021-924X (Linking)
VI  - 137
IP  - 3
DP  - 2005 Mar
TI  - Novel role of the small GTPase Rheb: its implication in endocytic pathway 
      independent of the activation of mammalian target of rapamycin.
PG  - 423-30
AB  - The Ras-homologous GTPase Rheb that is conserved from yeast to human appears to 
      be involved not only in cell growth but also in nutrient uptake. Recent 
      biochemical analysis revealed that tuberous sclerosis complex (TSC), a 
      GTPase-activating protein (GAP), deactivates Rheb and that phosphatidylinositol 
      3'-kinase (PI3k)-Akt/PKB kinase pathway activates Rheb through inhibition of the 
      GAP-mediated deactivation. Although mammalian target of rapamycin (mTOR) kinase 
      is implicated in the downstream target of Rheb, the direct effector(s) and exact 
      functions of Rheb have not been fully elucidated. Here we identified that Rheb 
      expression in cultured cells induces the formation of large cytoplasmic vacuoles, 
      which are characterized as late endocytic (late endosome- and lysosome-like) 
      components. The vacuole formation required the GTP form of Rheb, but not the 
      activation of the downstream mTOR kinase. These results suggest that Rheb 
      regulates endocytic trafficking pathway independent of the previously identified 
      mTOR pathway. The physiological roles of the two Rheb-dependent signaling 
      pathways are discussed in terms of nutrient uptake and cell growth or cell cycle 
      progression.
FAU - Saito, Kota
AU  - Saito K
AD  - Department of Physiological Chemistry, Graduate School of Pharmaceutical 
      Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033.
FAU - Araki, Yasuhiro
AU  - Araki Y
FAU - Kontani, Kenji
AU  - Kontani K
FAU - Nishina, Hiroshi
AU  - Nishina H
FAU - Katada, Toshiaki
AU  - Katada T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Biochem
JT  - Journal of biochemistry
JID - 0376600
RN  - 0 (Neuropeptides)
RN  - 0 (Proto-Oncogene Proteins)
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 (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)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cytoplasmic Vesicles/metabolism
MH  - Dogs
MH  - Endocytosis/*physiology
MH  - Endosomes/metabolism
MH  - Enzyme Activation
MH  - HeLa Cells
MH  - Humans
MH  - Lysosomes/metabolism
MH  - Monomeric GTP-Binding Proteins/*physiology
MH  - Neuropeptides/*physiology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Kinases/physiology
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Ras Homolog Enriched in Brain Protein
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
MH  - Tissue Distribution
MH  - Vacuoles/metabolism
EDAT- 2005/04/06 09:00
MHDA- 2005/08/27 09:00
CRDT- 2005/04/06 09:00
PHST- 2005/04/06 09:00 [pubmed]
PHST- 2005/08/27 09:00 [medline]
PHST- 2005/04/06 09:00 [entrez]
AID - 137/3/423 [pii]
AID - 10.1093/jb/mvi046 [doi]
PST - ppublish
SO  - J Biochem. 2005 Mar;137(3):423-30. doi: 10.1093/jb/mvi046.