An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways.

Takanari Inoue, Won Do Heo, Joshua S Grimley, Thomas J Wandless, Tobias Meyer
Author Information
  1. Takanari Inoue: Stanford University, Department of Molecular Pharmacology, Clark Center, 318 Campus Drive, Stanford, California 94305-5439, USA. jctinoue@stanford.edu

Abstract

We made substantial advances in the implementation of a rapamycin-triggered heterodimerization strategy. Using molecular engineering of different targeting and enzymatic fusion constructs and a new rapamycin analog, Rho GTPases were directly activated or inactivated on a timescale of seconds, which was followed by pronounced cell morphological changes. As signaling processes often occur within minutes, such rapid perturbations provide a powerful tool to investigate the role, selectivity and timing of Rho GTPase-mediated signaling processes.

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Grants

  1. R01 MH064801/NIMH NIH HHS
  2. R01 GM063702/NIGMS NIH HHS
  3. R01 MH095087/NIMH NIH HHS
  4. GM068589/NIGMS NIH HHS
  5. R01 GM068589/NIGMS NIH HHS
  6. R01 GM030179-24A1/NIGMS NIH HHS
  7. GM063702/NIGMS NIH HHS
  8. R01 GM030179/NIGMS NIH HHS

MeSH Term

Animals
Cell Membrane
Enzyme Inhibitors
Kinetics
Mice
NIH 3T3 Cells
Protein Engineering
Recombinant Fusion Proteins
Signal Transduction
Sirolimus
Translocation, Genetic
rho GTP-Binding Proteins

Chemicals

Enzyme Inhibitors
Recombinant Fusion Proteins
rho GTP-Binding Proteins
Sirolimus

Word Cloud

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