GβL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR Journal Article

Authors: Kim, D. H.; Sarbassov, D. D.; Ali, S. M.; Latek, R. R.; Guntur, K. V. P.; Erdjument-Bromage, H.; Tempst, P.; Sabatini, D. M.
Article Title: GβL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR
Abstract: 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.
Keywords: signal transduction; s6 kinase; carrier protein; human cell; genetics; nonhuman; molecular genetics; protein domain; protein function; proteins; metabolism; mammalia; cell growth; protein kinases; protein protein interaction; protein; protein binding; cell differentiation; enzyme activity; hela cell; hela cells; physiology; regulatory mechanism; amino acid sequence; molecular sequence data; signal peptide; intracellular signaling peptides and proteins; nucleotide sequence; mammalian target of rapamycin; carrier proteins; adaptor proteins, signal transducing; phosphoproteins; base sequence; cell size; protein structure, tertiary; protein subunit; protein subunits; eukaryotic cell; nutrient; isolation and purification; protein kinase; phosphotransferase; signal transducing adaptor protein; rapamycin; protein tertiary structure; sirolimus; phosphoprotein; macromolecule; macromolecular substances; eukaryotic cells; fk 506 binding protein; raptores; tacrolimus binding proteins; ribosomal protein s6 kinases, 70-kda; humans; human; article; raptor protein, human; eif4ebp1 protein, human; gbetal protein, human; ribosomal protein s6 kinase, 70kd, polypeptide 2
Journal Title: Molecular Cell
Volume: 11
Issue: 4
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2003-04-01
Start Page: 895
End Page: 904
Language: English
DOI: 10.1016/s1097-2765(03)00114-x
PUBMED: 12718876
PROVIDER: scopus
Notes: Export Date: 12 September 2014 -- Source: Scopus
Citation Impact
MSK Authors
  1. Paul J Tempst
    323 Tempst