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

Edited by Felix Wieland

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.

Structured summary

MINT-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)

Abbreviations: GAP, GTP hydrolase activating protein, PPIase, peptidyl-prolyl-cis/trans-isomerase, RBD, Ras binding domain

Keywords: Cell growth, FKBP38, Isomerase, mTORC1, Rheb, Translational control

a Department of Structural Biology, Max Planck Institute for Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany

b Max Planck Research Unit for Enzymology of Protein Folding, Weinbergweg 22, 06120 Halle, Germany

c 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.

1 These authors contributed equally to this work.

PII: S0014-5793(09)00114-8

doi:10.1016/j.febslet.2009.02.015

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