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Rho GTPases as Targets of Bacterial Protein Toxins

  • K. Aktories , G. Schmidt and I. Just
Published/Copyright: July 5, 2005
Biological Chemistry
From the journal Volume 381 Issue 5-6

Abstract

Several bacterial toxins target Rho GTPases, which constitute molecular switches in several signaling processes and master regulators of the actin cytoskeleton. The biological activities of Rho GTPases are blocked by C3-like transferases, which ADP-ribosylate Rho at Asn41, but not Rac or Cdc42. Large clostridial cytotoxins (e. g., Clostridium difficile toxin A and B) glucosylate Rho GTPases at Thr37 (Rho) or Thr35 (Rac/Cdc42), thereby inhibiting Rho functions by preventing effector coupling. The ‘injected’ toxins ExoS, YopE and SptP from Pseudomonas aeruginosa, Yersinia and Salmonella ssp., respectively, which are transferred into the eukaryotic target cells by the type-III secretion system, inhibit Rho functions by acting as Rho GAP proteins. Rho GTPases are activated by the cytotoxic necrotizing factors CNF1 and CNF2 from Escherichia coli and by the dermonecrotizing toxin DNT from B. bronchiseptica. These toxins deamidate/ transglutaminate Gln63 of Rho to block the intrinsic and GAP-stimulated GTP hydrolysis, thereby constitutively activating the GTPases. Rho GTPases are also activated by SopE, a type-III system injected protein from Salmonella ssp., that acts as a GEF protein.

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Published Online: 2005-07-05
Published in Print: 2000-06-21

Copyright © 2000 by Walter de Gruyter GmbH & Co. KG

Articles in the same Issue

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  2. Signal Transduction and Post-Transcriptional Gene Expression
  3. Regulation of GTPases in the Bacterial Translation Machinery
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  5. The Role of Heterotrimeric G Proteins in Platelet Activation
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