• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s.

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.

Pubmed ID: 16919458

Authors

  • Frias MA
  • Thoreen CC
  • Jaffe JD
  • Schroder W
  • Sculley T
  • Carr SA
  • Sabatini DM

Journal

Current biology : CB

Publication Data

September 19, 2006

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01 AI047389
  • Agency: NCI NIH HHS, Id: R01 CA103866

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Cell Line, Tumor
  • Humans
  • Insulin
  • Phosphorylation
  • Protein Binding
  • Protein Isoforms
  • Protein Kinases
  • Proto-Oncogene Proteins c-akt
  • Sirolimus
  • TOR Serine-Threonine Kinases