The switch I region of Rheb is critical for its interaction with FKBP38.
The Ras-like small GTPase Rheb is an upstream activator of the mammalian target of rapamycin (mTOR). It has recently been shown that Rheb activates mTOR by binding to its endogenous inhibitor FKBP38 and preventing it from association with mTOR. The interaction of Rheb with FKBP38 is controlled by its guanine nucleotide binding states, which are responsive to growth factor and amino acid conditions. In this study, we show that Rheb interacts with FKBP38 through a section within its switch I region that is equivalent to the effector domain of other Ras-like small GTPases. We find that the ability for Rheb to interact with FKBP38 correlates with its activity for mTOR activation. Our findings suggest that FKBP38 is a bona fide effector of Rheb and that the ability to interact with FKBP38 is important for Rheb as an activator of mTOR.
Ma
Dongzhu
D
Department of Pharmacology and Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
Bai
Xiaochun
X
Guo
Shuguang
S
Jiang
Yu
Y
D003600:Cytosol / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000737:chemistry; D017353:Gene Deletion; D006147:Guanine / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D008856:Microscopy, Fluorescence / Q000379:methods; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry*; D046912:Multiprotein Complexes; D009479:Neuropeptides / Q000737:chemistry*; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D011506:Proteins; D000076205:Ras Homolog Enriched in Brain Protein; D058570:TOR Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
C471205:FKBP8 protein, human; D046912:Multiprotein Complexes; D009479:Neuropeptides; D011506:Proteins; C490211:RHEB protein, human; D000076205:Ras Homolog Enriched in Brain Protein; D014157:Transcription Factors; D006147:Guanine; D011494:Protein Kinases; C546842:MTOR protein, human; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D020558:GTP Phosphohydrolases; D020559:Monomeric GTP-Binding Proteins; D022021:Tacrolimus Binding Proteins; C403485:tacrolimus binding protein 4