Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive.
The target of rapamycin (TOR) is a highly conserved protein kinase and a central controller of cell growth. In budding yeast, TOR is found in structurally and functionally distinct protein complexes: TORC1 and TORC2. A mammalian counterpart of TORC1 (mTORC1) has been described, but it is not known whether TORC2 is conserved in mammals. Here, we report that a mammalian counterpart of TORC2 (mTORC2) also exists. mTORC2 contains mTOR, mLST8 and mAVO3, but not raptor. Like yeast TORC2, mTORC2 is rapamycin insensitive and seems to function upstream of Rho GTPases to regulate the actin cytoskeleton. mTORC2 is not upstream of the mTORC1 effector S6K. Thus, two distinct TOR complexes constitute a primordial signalling network conserved in eukaryotic evolution to control the fundamental process of cell growth.
Jacinto
Estela
E
Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland.
Loewith
Robbie
R
Schmidt
Anja
A
Lin
Shuo
S
Rüegg
Markus A
MA
Hall
Alan
A
Hall
Michael N
MN
D000199:Actins / Q000502:physiology*; D000818:Animals; D018797:Cell Cycle Proteins; D002460:Cell Line; D003599:Cytoskeleton / Q000502:physiology*; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000502:physiology*; D020123:Sirolimus / Q000494:pharmacology*
D000199:Actins; D018797:Cell Cycle Proteins; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D020123:Sirolimus