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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Cell Membrane / drug effects
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Cell Membrane / metabolism*
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Enzyme Inhibitors
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Kinetics
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Mice
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NIH 3T3 Cells
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Protein Engineering / methods*
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / drug effects
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Signal Transduction / physiology*
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Sirolimus / pharmacology*
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Translocation, Genetic / genetics
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rho GTP-Binding Proteins / antagonists & inhibitors*
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rho GTP-Binding Proteins / metabolism*
Substances
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Enzyme Inhibitors
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Recombinant Fusion Proteins
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rho GTP-Binding Proteins
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Sirolimus