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

Uhlenbrock, Katharina; Weiwad, Matthias; Wetzker, Reinhard; Fischer, Gunter; Wittinghofer, Alfred; Rubio, Ignacio

doi:10.1016/j.febslet.2009.02.015

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Volume 583, Issue 6 , Pages 965-970, 18 March 2009

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

Edited by Felix Wieland

Katharina Uhlenbrock
- Department of Structural Biology, Max Planck Institute for Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany
- These authors contributed equally to this work.
Matthias Weiwad
- Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, 06120 Halle, Germany
Reinhard Wetzker
- Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Friedrich Schiller University, Hans-Knöll-Str. 2, 07745 Jena, Germany
Gunter Fischer
- Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, 06120 Halle, Germany
Alfred Wittinghofer
- Department of Structural Biology, Max Planck Institute for Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany
Ignacio Rubio
- Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Friedrich Schiller University, Hans-Knöll-Str. 2, 07745 Jena, Germany
- Corresponding author. Fax: +49 0 3641 9395602.
- These authors contributed equally to this work.

Received 29 January 2009; accepted 6 February 2009. published online 20 February 2009.

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.