mTOR and raptor are components of a signaling pathway that regulates mammalian cell growth in response to nutrients and growth factors. Here, we identify a member of this pathway, a protein named GβL that binds to the kinase domain of mTOR and stabilizes the interaction of raptor with mTOR. Like mTOR and raptor, GβL participates in nutrient- and growth factor-mediated signaling to S6K1, a downstream effector of mTOR, and in the control of cell size. The binding of GβL to mTOR strongly stimulates the kinase activity of mTOR toward S6K1 and 4E-BP1, an effect reversed by the stable interaction of raptor with mTOR. Interestingly, nutrients and rapamycin regulate the association between mTOR and raptor only in complexes that also contain GβL. Thus, we propose that the opposing effects on mTOR activity of the GβL- and raptor-mediated interactions regulate the mTOR pathway.
Bibliographical noteFunding Information:
This work was supported by grants from the NIH (R01 AI47389) and the G. Harold and Leila Y. Mathers Charitable Foundation to D.M.S. and fellowships from the Korea Science and Engineering Foundation and Human Frontier Science Program to D.-H.K., the Anna Fuller Fund to D.D.S., and the Howard Hughes Medical Institute to S.M.A.