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3 - Rho-activating toxins and growth regulation

Published online by Cambridge University Press:  15 September 2009

Gudula Schmidt
Affiliation:
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg
Klaus Aktories
Affiliation:
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg
Alistair J. Lax
Affiliation:
King's College London
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Summary

Low molecular mass GTPases of the Rho family are master regulators of the actin cytoskeleton and are involved in various signal transduction processes. They regulate the actin cytoskeleton and control transcriptional activation, cell cycle progression, cell transformation, and apoptosis. Rho GTPases are the eukaryotic targets of a variety of bacterial protein toxins that either inhibit or activate the Rho proteins. The cytotoxic necrotizing factors CNF1 and 2 from Escherichia coli and the dermonecrotic toxin DNT from Bordetella species are Rho-activating toxins. Whereas CNFs cause deamidation of Rho proteins, DNT deamidates and/or transglutaminates the GTPases by attachment of polyamines. Both deamidation and transglutamination cause persistent activation of Rho GTPases and subsequent changes in processes governed by the GTPases.

RHO GTPASES

Rho GTPases belong to the Ras superefmily of low molecular mass GTPases and are molecular switches in various signalling pathways. Like all members of GTP-binding proteins, they are active in the GTP bound form and inactive with GDP bound. Activation occurs by GDP/GTP exchange catalysed by guanine nucleotide exchange factors (GEFs) and is inhibited by binding of guanine nucleotide dissociation inhibitors (GDIs). Inactivation by hydrolysis of the bound GTP is catalysed by GTPase activating proteins (GAPs) (Symons and Settleman, 2000).

Rho GTPases are ubiquitously expressed. The members (>15) of the Rho family of GTPases, including RhoA, B, C, D, E, and G, Cdc42, Rac1, 2, and 3, share more than 50% sequence identity. The GTPases have been described as important regulators of the actin cytoskeleton.

Type
Chapter
Information
Bacterial Protein Toxins
Role in the Interference with Cell Growth Regulation
, pp. 33 - 52
Publisher: Cambridge University Press
Print publication year: 2005

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  • Rho-activating toxins and growth regulation
    • By Gudula Schmidt, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg, Klaus Aktories, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg
  • Edited by Alistair J. Lax, King's College London
  • Book: Bacterial Protein Toxins
  • Online publication: 15 September 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511546280.004
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  • Rho-activating toxins and growth regulation
    • By Gudula Schmidt, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg, Klaus Aktories, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg
  • Edited by Alistair J. Lax, King's College London
  • Book: Bacterial Protein Toxins
  • Online publication: 15 September 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511546280.004
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  • Rho-activating toxins and growth regulation
    • By Gudula Schmidt, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg, Klaus Aktories, Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Albert-Ludwigs-Universität Freiburg
  • Edited by Alistair J. Lax, King's College London
  • Book: Bacterial Protein Toxins
  • Online publication: 15 September 2009
  • Chapter DOI: https://doi.org/10.1017/CBO9780511546280.004
Available formats
×