Reassessment of the role of FKBP38 in the Rheb/mTORC1 pathway

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.Structured summaryMINT-6946532: Ral (uniprotkb:P11233) binds (MI:0407) to Ha-Ras (uniprotkb:P01112) by pull down (MI:0096)MINT-6946500: RAF (uniprotkb:P04049) binds (MI:0407) to RHEB2 (uniprotkb:Q15382) by pull down (MI:0096)MINT-6946517: RAF (uniprotkb:P04049) binds (MI:0407) to Ha-Ras (uniprotkb:P01112) by pull down (MI:0096)