mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery
Authors: Robert R Latek
Hediye Erdjument-Bromage
D D Sarbassov
Do-Hyung Kim
Jessie E King
Paul Tempst
David M Sabatini
Siraj M Ali
Journal: Cell (2002)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: mTOR; raptor; nutrient signaling; cell growth; S6K1
Affiliations: Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, MA 02142, USA.

Abstract:  mTOR/RAFT1/FRAP is the target of the immunosuppressive drug rapamycin and the central component of a nutrient- and hormone-sensitive signaling pathway that regulates cell growth. We report that mTOR forms a stoichiometric complex with raptor, an evolutionarily conserved protein with at least two roles in the mTOR pathway. Raptor has a positive role in nutrient-stimulated signaling to the downstream effector S6K1, maintenance of cell size, and mTOR protein expression. The association of raptor with mTOR also negatively regulates the mTOR kinase activity. Conditions that repress the pathway, such as nutrient deprivation and mitochondrial uncoupling, stabilize the mTOR-raptor association and inhibit mTOR kinase activity. We propose that raptor is a missing component of the mTOR pathway that through its association with mTOR regulates cell size in response to nutrient levels. 

Retracted: No

PubPeer comments:
 Figure 4A. https: imgur.com 3luiT4F , 
 Figure 5C. https: imgur.com qvxZQec , 
 Thank you for your comments. This almost 18-year-old paper describes the discovery of raptor, the defining component of the protein complex we now call mTOR Complex 1 (mTORC1). We showed that mTORC1u2019s kinase activity is rapamycin-sensitive and that mTORC1 regulates cell growth. We now appreciate that mTORC1 is the major growth regulator in eukaryotes. The existence of mTORC1 and its role in growth control has been validated by dozens of labs in diverse organisms using a variety of approaches, including biochemical and genetic methods, and, most recently, structural ones. Hydrophis Spiralis points to what is a clear gel splice in Figure 4A for the anti-myc blot and a less clear one in Figure 5C for the phospho-S6K1 blot. There is also likely a splice in the total S6K1 blot in Figure 5C, but it is much harder to see because the blot is less exposed. As was common practice in 2002, the splice junctions are not indicated by lines. Without going back to the original films, which are in an offsite repository, I cannot be sure why splices were made but the usual reason is because intervening samples that we deemed not relevant to the final figure had to be removed (for example, uninformative mTOR mutants or additional negative controls in Figure 4A). Not all blots will have been spliced because in many cases the gels for certain blots had to be rerun as there were issues with the processing of the gel or immunoblot, which provided an opportunity to analyze only the samples relevant to the final figure. Please note that the presence of a gel splice has no impact on the validity of the data shown or our conclusions, which, as noted above, have been validated by others. Best wishes, David M. Sabatini , 
 #3  Hydrophis Spiralis points to what is a clear gel splice in Figure 4A for the anti-myc blot and a less clear one in Figure 5C for the phospho-S6K1 blot. There are no splices in the mTOR or raptor panels which are in the same figure.  Hydrophis Spiralis points to what is a clear gel splice in Figure 4A for the anti-myc blot .. There is no splice in the anti-HA blot. , 
 Indeed, please read my response carefully. Thanks, David M. Sabatini ,