4.8 Article

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

Journal

NATURE METHODS
Volume 2, Issue 6, Pages 415-418

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/NMETH763

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Funding

  1. NIGMS NIH HHS [R01 GM030179, R01 GM063702, GM068589, R01 GM068589, R01 GM030179-24A1, GM063702] Funding Source: Medline
  2. NIMH NIH HHS [R01 MH064801, R01 MH095087] Funding Source: Medline

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We made substantial advances in the implementation of a rapa mycin-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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