PMID- 23732640
OWN - NLM
STAT- MEDLINE
DCOM- 20140403
LR  - 20211203
IS  - 1469-7793 (Electronic)
IS  - 0022-3751 (Print)
IS  - 0022-3751 (Linking)
VI  - 591
IP  - 18
DP  - 2013 Sep 15
TI  - Eccentric contractions increase the phosphorylation of tuberous sclerosis 
      complex-2 (TSC2) and alter the targeting of TSC2 and the mechanistic target of 
      rapamycin to the lysosome.
PG  - 4611-20
LID - 10.1113/jphysiol.2013.256339 [doi]
AB  -   The goal of this study was to determine whether the mechanical activation of 
      mechanistic target of rapamycin (mTOR) signalling is associated with changes in 
      phosphorylation of tuberous sclerosis complex-2 (TSC2) and targeting of mTOR and 
      TSC2 to the lysosome. As a source of mechanical stimulation, mouse skeletal 
      muscles were subjected to eccentric contractions (ECs). The results demonstrated 
      that ECs induced hyper-phosphorylation of TSC2 and at least part of this increase 
      occurred on residue(s) that fall within RxRxxS/T consensus motif(s). Furthermore, 
      in control muscles, we found that both mTOR and TSC2 are highly enriched at the 
      lysosome. Intriguingly, ECs enhanced the lysosomal association of mTOR and almost 
      completely abolished the lysosomal association of TSC2. Based on these results, 
      we developed a new model that could potentially explain how mechanical stimuli 
      activate mTOR signalling. Furthermore, this is the first study to reveal that the 
      activation of mTOR is associated with the translocation of TSC2 away from the 
      lysosome. Since a large number of signalling pathways rely on TSC2 to control 
      mTOR signalling, our results have potentially revealed a fundamental mechanism 
      via which not only mechanical, but also various other types of stimuli, control 
      mTOR signalling.
FAU - Jacobs, Brittany L
AU  - Jacobs BL
AD  - T. A. Hornberger: Department of Comparative Biosciences, 2015 Linden Drive, 
      Madison, WI 53706, USA. thornb1@svm.vetmed.wisc.edu.
FAU - You, Jae-Sung
AU  - You JS
FAU - Frey, John W
AU  - Frey JW
FAU - Goodman, Craig A
AU  - Goodman CA
FAU - Gundermann, David M
AU  - Gundermann DM
FAU - Hornberger, Troy A
AU  - Hornberger TA
LA  - eng
GR  - R01 AR057347/AR/NIAMS NIH HHS/United States
GR  - AR057347/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20130603
PL  - England
TA  - J Physiol
JT  - The Journal of physiology
JID - 0266262
RN  - 0 (Tsc2 protein, mouse)
RN  - 0 (Tuberous Sclerosis Complex 2 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
CIN - J Physiol. 2013 Sep 15;591(18):4369-70. PMID: 24037132
MH  - Amino Acid Motifs
MH  - Animals
MH  - Cell Line
MH  - Lysosomes/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - *Muscle Contraction
MH  - Muscle, Skeletal/*metabolism/physiology
MH  - Phosphorylation
MH  - Protein Transport
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tuberous Sclerosis Complex 2 Protein
MH  - Tumor Suppressor Proteins/chemistry/*metabolism
PMC - PMC3784202
EDAT- 2013/06/05 06:00
MHDA- 2014/04/04 06:00
PMCR- 2014/09/15
CRDT- 2013/06/05 06:00
PHST- 2013/06/05 06:00 [entrez]
PHST- 2013/06/05 06:00 [pubmed]
PHST- 2014/04/04 06:00 [medline]
PHST- 2014/09/15 00:00 [pmc-release]
AID - jphysiol.2013.256339 [pii]
AID - 10.1113/jphysiol.2013.256339 [doi]
PST - ppublish
SO  - J Physiol. 2013 Sep 15;591(18):4611-20. doi: 10.1113/jphysiol.2013.256339. Epub 
      2013 Jun 3.