PMID- 11884412
OWN - NLM
STAT- MEDLINE
DCOM- 20020716
LR  - 20220316
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 20
DP  - 2002 May 17
TI  - Control of Ser2448 phosphorylation in the mammalian target of rapamycin by 
      insulin and skeletal muscle load.
PG  - 17657-62
AB  - We have investigated the effects of insulin, amino acids, and the degree of 
      muscle loading on the phosphorylation of Ser(2448), a site in the mammalian 
      target of rapamycin (mTOR) phosphorylated by protein kinase B (PKB) in vitro. 
      Phosphorylation was assessed by immunoblotting with a phosphospecific antibody 
      (anti-Ser(P)(2448)) and with mTAb1, an activating antibody whose binding is 
      inhibited by phosphorylation in the region of mTOR that contains Ser(2448). 
      Incubating rat diaphragm muscles with insulin increased Ser(2448) phosphorylation 
      but did not change the total amount of mTOR. Insulin, but not amino acids, 
      activated PKB, as evidenced by increased phosphorylation of both Ser(308) and 
      Thr(473) in the kinase. Ser(2448) phosphorylation was also modulated by 
      muscle-loading. Overloading the rat plantaris muscle by synergist muscle 
      ablation, which promotes hypertrophy of the plantaris muscle, increased Ser(2448) 
      phosphorylation. In contrast, unloading the gastrocnemius muscle by hindlimb 
      suspension, which promotes atrophy of the muscle, decreased Ser(2448) 
      phosphorylation, an effect that was fully reversible. Neither overloading nor 
      hindlimb suspension significantly changed the total amount of mTOR. In summary, 
      our results demonstrate that atrophy and hypertrophy of skeletal muscle are 
      associated with decreases and increases in Ser(2448) phosphorylation, suggesting 
      that modulation of this site may have an important role in the control of protein 
      synthesis.
FAU - Reynolds, Thomas H 4th
AU  - Reynolds TH 4th
AD  - Department of Pharmacology, University of Virginia Health System, 
      Charlottesville, Virginia 22908-0735, USA.
FAU - Bodine, Sue C
AU  - Bodine SC
FAU - Lawrence, John C Jr
AU  - Lawrence JC Jr
LA  - eng
GR  - AR-41180/AR/NIAMS NIH HHS/United States
GR  - DK-52753/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020307
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Amino Acids)
RN  - 0 (HIV Envelope Protein gp120)
RN  - 0 (Insulin)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (TAB1 protein, human)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, rat)
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  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Amino Acids/metabolism
MH  - Animals
MH  - Diaphragm/enzymology/metabolism
MH  - HIV Envelope Protein gp120/immunology/metabolism
MH  - Insulin/*metabolism
MH  - Muscle, Skeletal/*physiology
MH  - Phosphorylation
MH  - Protein Biosynthesis
MH  - Protein Kinases/metabolism/*physiology
MH  - *Protein Serine-Threonine Kinases
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-akt
MH  - Rats
MH  - Recombinant Fusion Proteins/immunology/metabolism
MH  - Serine/*metabolism
MH  - Sirolimus/*metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Weight-Bearing
EDAT- 2002/03/09 10:00
MHDA- 2002/07/18 10:01
CRDT- 2002/03/09 10:00
PHST- 2002/03/09 10:00 [pubmed]
PHST- 2002/07/18 10:01 [medline]
PHST- 2002/03/09 10:00 [entrez]
AID - S0021-9258(20)85256-9 [pii]
AID - 10.1074/jbc.M201142200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 May 17;277(20):17657-62. doi: 10.1074/jbc.M201142200. Epub 2002 
      Mar 7.