title: Reassessment of the role of FKBP38 in the Rheb/mTORC1 pathway.
abstract: The small G-protein Rheb regulates cell growth via the mTORC1 complex by incompletely understood mechanisms. Recent studies document that Rheb activates mTORC1 via direct, GTP-dependent interaction with the peptidyl-prolyl-cis/trans-isomerase FKBP38, which is proposed to act as an inhibitor of mTORC1. We have conducted a comprehensive biochemical characterization of the Rheb/FKBP38 interaction. Using three different in vitro assays we did not detect an interaction between Rheb and FKBP38. Cell biological experiments illustrate that FKBP38 plays only a very minor, if any, role in mTORC1 activation. Our data document that FKBP38 is not the long-sought Rheb effector linking Rheb to mTORC1 activation.
authors.affiliation: Department of Structural Biology, Max Planck Institute for Molecular Physiology, Dortmund, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Uhlenbrock
authors.forename: Matthias
authors.initials: M
authors.lastname: Weiwad
authors.forename: Reinhard
authors.initials: R
authors.lastname: Wetzker
authors.forename: Gunter
authors.initials: G
authors.lastname: Fischer
authors.forename: Alfred
authors.initials: A
authors.lastname: Wittinghofer
authors.forename: Ignacio
authors.initials: I
authors.lastname: Rubio
mesh_terms: D002478:Cells, Cultured; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D000076222:Mechanistic Target of Rapamycin Complex 1; D020559:Monomeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D046912:Multiprotein Complexes; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D011506:Proteins; D034741:RNA, Small Interfering / Q000494:pharmacology; D000076205:Ras Homolog Enriched in Brain Protein; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D022021:Tacrolimus Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*; D015533:Transcriptional Activation / Q000187:drug effects; D014162:Transfection
chemical_list: C471205:FKBP8 protein, human; D007328:Insulin; D046912:Multiprotein Complexes; D009479:Neuropeptides; D011506:Proteins; C490211:RHEB protein, human; D034741:RNA, Small Interfering; D000076205:Ras Homolog Enriched in Brain Protein; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000076222:Mechanistic Target of Rapamycin Complex 1; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; D020559:Monomeric GTP-Binding Proteins; D022021:Tacrolimus Binding Proteins