PMID- 17991864
OWN - NLM
STAT- MEDLINE
DCOM- 20071123
LR  - 20220225
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Linking)
VI  - 318
IP  - 5852
DP  - 2007 Nov 9
TI  - Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38.
PG  - 977-80
AB  - The mammalian target of rapamycin, mTOR, is a central regulator of cell growth. 
      Its activity is regulated by Rheb, a Ras-like small guanosine triphosphatase 
      (GTPase), in response to growth factor stimulation and nutrient availability. We 
      show that Rheb regulates mTOR through FKBP38, a member of the FK506-binding 
      protein (FKBP) family that is structurally related to FKBP12. FKBP38 binds to 
      mTOR and inhibits its activity in a manner similar to that of the 
      FKBP12-rapamycin complex. Rheb interacts directly with FKBP38 and prevents its 
      association with mTOR in a guanosine 5'-triphosphate (GTP)-dependent manner. Our 
      findings suggest that FKBP38 is an endogenous inhibitor of mTOR, whose inhibitory 
      activity is antagonized by Rheb in response to growth factor stimulation and 
      nutrient availability.
FAU - Bai, Xiaochun
AU  - Bai X
AD  - Department of Pharmacology, University of Pittsburgh School of Medicine, E1357 
      Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
FAU - Ma, Dongzhu
AU  - Ma D
FAU - Liu, Anling
AU  - Liu A
FAU - Shen, Xiaoyun
AU  - Shen X
FAU - Wang, Qiming J
AU  - Wang QJ
FAU - Liu, Yongjian
AU  - Liu Y
FAU - Jiang, Yu
AU  - Jiang Y
LA  - eng
GR  - R01 CA129821/CA/NCI NIH HHS/United States
GR  - R01 GM068832/GM/NIGMS NIH HHS/United States
GR  - GM068832/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Amino Acids)
RN  - 0 (Culture Media)
RN  - 0 (FKBP8 protein, human)
RN  - 0 (Insulin)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Mutant Proteins)
RN  - 0 (Neuropeptides)
RN  - 0 (Proteins)
RN  - 0 (RHEB protein, human)
RN  - 0 (Ras Homolog Enriched in Brain Protein)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factors)
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 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
RN  - EC 5.2.1.- (Tacrolimus Binding Proteins)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
CIN - Science. 2007 Nov 9;318(5852):926-7. PMID: 17991850
MH  - Amino Acids/metabolism
MH  - Cell Line
MH  - Culture Media
MH  - Guanosine Triphosphate/metabolism
MH  - Humans
MH  - Insulin/metabolism
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Monomeric GTP-Binding Proteins/*metabolism
MH  - Multiprotein Complexes
MH  - Mutant Proteins/metabolism
MH  - Neuropeptides/*metabolism
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Kinases/chemistry/*metabolism
MH  - Protein Structure, Tertiary
MH  - Proteins
MH  - Ras Homolog Enriched in Brain Protein
MH  - Recombinant Proteins/metabolism
MH  - Serum
MH  - Signal Transduction
MH  - Sirolimus/metabolism/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Tacrolimus Binding Proteins/antagonists & inhibitors/*metabolism
MH  - Transcription Factors/metabolism
EDAT- 2007/11/10 09:00
MHDA- 2007/12/06 09:00
CRDT- 2007/11/10 09:00
PHST- 2007/11/10 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/11/10 09:00 [entrez]
AID - 318/5852/977 [pii]
AID - 10.1126/science.1147379 [doi]
PST - ppublish
SO  - Science. 2007 Nov 9;318(5852):977-80. doi: 10.1126/science.1147379.