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

Curr Biol. 2006 Sep 19;16(18):1865-70. doi: 10.1016/j.cub.2006.08.001. Epub 2006 Aug 17.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / chemistry
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Adaptor Proteins, Signal Transducing / physiology
  • Cell Line, Tumor
  • Humans
  • Insulin / metabolism
  • Phosphorylation
  • Protein Binding / drug effects
  • Protein Isoforms / chemistry
  • Protein Isoforms / metabolism
  • Protein Isoforms / physiology
  • Protein Kinases / chemistry
  • Protein Kinases / metabolism*
  • Proto-Oncogene Proteins c-akt / chemistry
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases

Substances

  • Adaptor Proteins, Signal Transducing
  • Insulin
  • MAPKAP1 protein, human
  • Protein Isoforms
  • Protein Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Sirolimus