PMID- 16919458
OWN - NLM
STAT- MEDLINE
DCOM- 20061030
LR  - 20211203
IS  - 0960-9822 (Print)
IS  - 0960-9822 (Linking)
VI  - 16
IP  - 18
DP  - 2006 Sep 19
TI  - mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three 
      distinct mTORC2s.
PG  - 1865-70
AB  - The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that 
      participates in at least two distinct multiprotein complexes, mTORC1 and mTORC2 . 
      These complexes play important roles in the regulation of cell growth, 
      proliferation, survival, and metabolism. mTORC2 is a hydrophobic motif kinase for 
      the cell-survival protein Akt/PKB and, here, we identify mSin1 as a component of 
      mTORC2 but not mTORC1. mSin1 is necessary for the assembly of mTORC2 and for its 
      capacity to phosphorylate Akt/PKB. Alternative splicing generates at least five 
      isoforms of the mSin1 protein , three of which assemble into mTORC2 to generate 
      three distinct mTORC2s. Even though all mTORC2s can phosphorylate Akt/PKB in 
      vitro, insulin regulates the activity of only two of them. Thus, we propose that 
      cells contain several mTORC2 flavors that may phosphorylate Akt/PKB in response 
      to different signals.
FAU - Frias, Maria A
AU  - Frias MA
AD  - Whitehead Institute for Biomedical Research and Department of Biology, 
      Massachusetts Institute of Technology, Nine Cambridge Center, Cambridge, 
      Massachusetts 02142, USA.
FAU - Thoreen, Carson C
AU  - Thoreen CC
FAU - Jaffe, Jacob D
AU  - Jaffe JD
FAU - Schroder, Wayne
AU  - Schroder W
FAU - Sculley, Tom
AU  - Sculley T
FAU - Carr, Steven A
AU  - Carr SA
FAU - Sabatini, David M
AU  - Sabatini DM
LA  - eng
GR  - R01 AI047389/AI/NIAID NIH HHS/United States
GR  - R01 CA103866/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060817
PL  - England
TA  - Curr Biol
JT  - Current biology : CB
JID - 9107782
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Insulin)
RN  - 0 (MAPKAP1 protein, human)
RN  - 0 (Protein Isoforms)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
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/chemistry/*metabolism/physiology
MH  - Cell Line, Tumor
MH  - Humans
MH  - Insulin/metabolism
MH  - Phosphorylation
MH  - Protein Binding/drug effects
MH  - Protein Isoforms/chemistry/metabolism/physiology
MH  - Protein Kinases/chemistry/*metabolism
MH  - Proto-Oncogene Proteins c-akt/chemistry/*metabolism
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases
EDAT- 2006/08/22 09:00
MHDA- 2006/10/31 09:00
CRDT- 2006/08/22 09:00
PHST- 2006/05/25 00:00 [received]
PHST- 2006/07/31 00:00 [revised]
PHST- 2006/08/01 00:00 [accepted]
PHST- 2006/08/22 09:00 [pubmed]
PHST- 2006/10/31 09:00 [medline]
PHST- 2006/08/22 09:00 [entrez]
AID - S0960-9822(06)01974-9 [pii]
AID - 10.1016/j.cub.2006.08.001 [doi]
PST - ppublish
SO  - Curr Biol. 2006 Sep 19;16(18):1865-70. doi: 10.1016/j.cub.2006.08.001. Epub 2006 
      Aug 17.