PMID- 15723049
OWN - NLM
STAT- MEDLINE
DCOM- 20050331
LR  - 20211203
IS  - 1465-7392 (Print)
IS  - 1465-7392 (Linking)
VI  - 7
IP  - 3
DP  - 2005 Mar
TI  - Atrophy of S6K1(-/-) skeletal muscle cells reveals distinct mTOR effectors for 
      cell cycle and size control.
PG  - 286-94
AB  - The mammalian target of rapamycin (mTOR) and Akt proteins regulate various steps 
      of muscle development and growth, but the physiological relevance and the 
      downstream effectors are under investigation. Here we show that S6 kinase 1 
      (S6K1), a protein kinase activated by nutrients and insulin-like growth factors 
      (IGFs), is essential for the control of muscle cytoplasmic volume by Akt and 
      mTOR. Deletion of S6K1 does not affect myoblast cell proliferation but reduces 
      myoblast size to the same extent as that observed with mTOR inhibition by 
      rapamycin. In the differentiated state, S6K1(-/-) myotubes have a normal number 
      of nuclei but are smaller, and their hypertrophic response to IGF1, nutrients and 
      membrane-targeted Akt is blunted. These growth defects reveal that mTOR requires 
      distinct effectors for the control of muscle cell cycle and size, potentially 
      opening new avenues of therapeutic intervention against neoplasia or muscle 
      atrophy.
FAU - Ohanna, Mickael
AU  - Ohanna M
AD  - Inserm, Avenir, U584, Universite Paris 5, Faculte de Medecine Necker-Enfants 
      Malades, 156 rue de Vaugirard, Paris, F-75730, France.
FAU - Sobering, Andrew K
AU  - Sobering AK
FAU - Lapointe, Thomas
AU  - Lapointe T
FAU - Lorenzo, Lazaro
AU  - Lorenzo L
FAU - Praud, Christophe
AU  - Praud C
FAU - Petroulakis, Emmanuel
AU  - Petroulakis E
FAU - Sonenberg, Nahum
AU  - Sonenberg N
FAU - Kelly, Paul A
AU  - Kelly PA
FAU - Sotiropoulos, Athanassia
AU  - Sotiropoulos A
FAU - Pende, Mario
AU  - Pende M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050220
PL  - England
TA  - Nat Cell Biol
JT  - Nature cell biology
JID - 100890575
RN  - 0 (Drug Combinations)
RN  - 0 (Laminin)
RN  - 0 (Proteoglycans)
RN  - 0 (Somatomedins)
RN  - 119978-18-6 (matrigel)
RN  - 147336-22-9 (Green Fluorescent Proteins)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (ribosomal protein S6 kinase, 70kD, polypeptide 2)
SB  - IM
MH  - Animals
MH  - Atrophy
MH  - Body Weight
MH  - Cell Differentiation
MH  - Cell Line
MH  - Cells, Cultured
MH  - Collagen/pharmacology
MH  - Drug Combinations
MH  - Gene Deletion
MH  - Genetic Vectors
MH  - Genotype
MH  - Green Fluorescent Proteins/metabolism
MH  - Homozygote
MH  - Humans
MH  - Immunoblotting
MH  - Laminin/pharmacology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Models, Biological
MH  - Muscle, Skeletal/*metabolism
MH  - Muscles/pathology
MH  - Plasmids/metabolism
MH  - Protein Binding
MH  - Protein Kinases/*metabolism
MH  - Proteoglycans/pharmacology
MH  - Retroviridae/genetics
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*genetics/*physiology
MH  - Signal Transduction
MH  - Somatomedins/metabolism
MH  - TOR Serine-Threonine Kinases
MH  - Time Factors
MH  - Transfection
EDAT- 2005/02/22 09:00
MHDA- 2005/04/01 09:00
CRDT- 2005/02/22 09:00
PHST- 2004/12/06 00:00 [received]
PHST- 2005/01/17 00:00 [accepted]
PHST- 2005/02/22 09:00 [pubmed]
PHST- 2005/04/01 09:00 [medline]
PHST- 2005/02/22 09:00 [entrez]
AID - ncb1231 [pii]
AID - 10.1038/ncb1231 [doi]
PST - ppublish
SO  - Nat Cell Biol. 2005 Mar;7(3):286-94. doi: 10.1038/ncb1231. Epub 2005 Feb 20.