PMID- 11729323
OWN - NLM
STAT- MEDLINE
DCOM- 20011231
LR  - 20220408
IS  - 0036-8075 (Print)
IS  - 0036-8075 (Linking)
VI  - 294
IP  - 5548
DP  - 2001 Nov 30
TI  - Phosphatidic acid-mediated mitogenic activation of mTOR signaling.
PG  - 1942-5
AB  - The mammalian target of rapamycin (mTOR) governs cell growth and proliferation by 
      mediating the mitogen- and nutrient-dependent signal transduction that regulates 
      messenger RNA translation. We identified phosphatidic acid (PA) as a critical 
      component of mTOR signaling. In our study, mitogenic stimulation of mammalian 
      cells led to a phospholipase D-dependent accumulation of cellular PA, which was 
      required for activation of mTOR downstream effectors. PA directly interacted with 
      the domain in mTOR that is targeted by rapamycin, and this interaction was 
      positively correlated with mTOR's ability to activate downstream effectors. The 
      involvement of PA in mTOR signaling reveals an important function of this lipid 
      in signal transduction and protein synthesis, as well as a direct link between 
      mTOR and mitogens. Furthermore, these studies suggest a potential mechanism for 
      the in vivo actions of the immunosuppressant rapamycin.
FAU - Fang, Y
AU  - Fang Y
AD  - Department of Cell and Structural Biology, University of Illinois at 
      Urbana-Champaign, 601 South Goodwin Avenue, B107, Urbana, IL 61801, USA.
FAU - Vilella-Bach, M
AU  - Vilella-Bach M
FAU - Bachmann, R
AU  - Bachmann R
FAU - Flanigan, A
AU  - Flanigan A
FAU - Chen, J
AU  - Chen J
LA  - eng
GR  - GM58064/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.
PL  - United States
TA  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Butanols)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (EIF4EBP1 protein, human)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Mitogens)
RN  - 0 (Phosphatidic Acids)
RN  - 0 (Phosphoproteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.4.4 (Phospholipase D)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Butanols/pharmacology
MH  - Carrier Proteins/metabolism
MH  - Cell Cycle Proteins
MH  - Cell Line
MH  - Culture Media, Serum-Free
MH  - Enzyme Activation/drug effects
MH  - Humans
MH  - Immunosuppressive Agents/pharmacology
MH  - Mitogens/*pharmacology
MH  - Phosphatidic Acids/*metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phospholipase D/metabolism
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Binding
MH  - Protein Kinases/chemistry/*metabolism
MH  - Protein Structure, Tertiary
MH  - Ribosomal Protein S6 Kinases/metabolism
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
MH  - Time Factors
EDAT- 2001/12/01 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/12/01 10:00
PHST- 2001/12/01 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/12/01 10:00 [entrez]
AID - 294/5548/1942 [pii]
AID - 10.1126/science.1066015 [doi]
PST - ppublish
SO  - Science. 2001 Nov 30;294(5548):1942-5. doi: 10.1126/science.1066015.