The polybasic region of Rho GTPases defines the cleavage by <i>Yersinia enterocolitica</i> outer protein T (YopT)

Fueller, Florian; Schmidt, Gudula

doi:10.1110/ps.035386.108

Cited by 16 publications

(13 citation statements)

References 28 publications

(25 reference statements)

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“…Figure 3 shows that YopT treatment led to about 60% loss of median fluorescence intensity in the case of RhoA, followed by 50% for RhoC, 40% for Rac1, 30% for Rac2, and only about 15% for Cdc42 (isoform 2) compared to non-treated GTPases. These results show the differential affects of YopT on Rho GTPases which is in accordance with results reported by Fueller and Schmidt, 2008. In addition, the loss of the isoprenyl moiety of a distinct Rho GTPase leads to the decrease in relative binding affinity to Rho GDI and supports the findings described in the previous section.…”

Section: Treatment Of Rho Gtpases With Yopt Differentially Affects Thsupporting

confidence: 92%

“…Rho GTPases post-translationally modified at their C-terminus have previously been shown to be differentially sensitive [RhoA > Rac1 > Cdc42 (isoform 1)] to proteolytic cleavage upstream of the isoprenylated, terminal cysteine residue by the cysteine protease YopT (Fueller and Schmidt, 2008). Therefore, the five Rho GTPases examined in this study were treated with recombinant YopT and used to perform the Rho GTPase-Rho GDIa interaction assay (Figure 1, b).…”

Section: Treatment Of Rho Gtpases With Yopt Differentially Affects Thmentioning

confidence: 99%

“…One of these effectors, YopT, a cysteine protease, cleaves the isoprenyl moiety of the Rho GTPases directly at the C-terminal cysteine. This leads to the release of the active GTPases from the membrane, and the resultant inactivation disrupts the actin cytoskeleton of the target cells and leads to cell rounding (Shao et al, 2002;Aepfelbacher et al, 2003;Shao et al, 2003;Fueller et al, 2006;Fueller and Schmidt, 2008;Shao, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Bead‐based protein–protein interaction assays for the analysis of Rho GTPase signaling

Rimmele

Gierschik

Joos

et al. 2010

J of Molecular Recognition

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Bead-based interaction assays are excellently suited to study protein-protein interactions, as they require only minimal amounts of sample material. Miniaturized protein-protein interaction assays were designed to analyze Rho GTPase activation based on its interaction with Rho GDI or p21-activated kinase (PAK).Rho GDI plays a key role in the regulation of a variety of cellular functions through its interaction with Rho GTPases. Rho GDI is frequently overexpressed in many human cancers. Therefore, there is a growing and as yet unfulfilled demand for screening assays to identify biologically active compounds that may inhibit the Rho GTPase-Rho GDI interaction. Bead-based interaction assays provide an interesting alternative that facilitate such assays to be performed faster with only small amounts of material compared to routinely used co-immunoprecipitation followed by Western Blot analysis.Bead-based protein interaction assays for overexpressed HA-tagged Rho GTPases were established to study the GTPγS-dependent interaction of five different Rho GTPases with the regulatory protein Rho GDIα and the downstream effector PAK1. In addition, it was demonstrated that the ability of Rho GTPases to interact with Rho GDI in this experimental system was markedly, but differentially sensitive to post-translational modification of their carboxyl terminus. Importantly, this modification also notably affected the ability of Rac1 and Rac2, but not of Cdc42, to interact with PAK1.

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Section: Treatment Of Rho Gtpases With Yopt Differentially Affects Thsupporting

confidence: 92%

Section: Treatment Of Rho Gtpases With Yopt Differentially Affects Thmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bead‐based protein–protein interaction assays for the analysis of Rho GTPase signaling

Rimmele

Gierschik

Joos

et al. 2010

J of Molecular Recognition

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“…The Rho GTPases are key signaling molecules involved in remodeling the actin cytoskeleton to mediate phagocytosis [48,49] . YopT has been shown to cleave the post-translationally modified RhoA, Rac1, and Cdc42 in vitro [50] . However, the enzymatic activity of YopT appears to be more selective in targeting different Rho protein(s) depending on the cell type and subcellular localization of the Rho proteins [35,51] .…”

Section: Yopt Targets the Rho Family Of Gtpasesmentioning

confidence: 99%

Yersiniatype III effectors perturb host innate immune responses

Pha

Navarro

2016

WJBC

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The innate immune system is the first line of defense against invading pathogens. Innate immune cells recognize molecular patterns from the pathogen and mount a response to resolve the infection. The production of proinflammatory cytokines and reactive oxygen species, phagocytosis, and induced programmed cell death are processes initiated by innate immune cells in order to combat invading pathogens. However, pathogens have evolved various virulence mechanisms to subvert these responses. One strategy utilized by Gram-negative bacterial pathogens is the deployment of a complex machine termed the type Ⅲ secretion system (T3SS). The T3SS is composed of a syringe-like needle structure and the effector proteins that are injected directly into a target host cell to disrupt a cellular response. The Multisite autophosphorylation by YpkA to activate its kinase domain was also shown and postulated to serve as a mechanism to bypass regulation by host phosphatases. In addition, novel Yersinia effector protein targets, such as caspase-1, and signaling pathways including activation of the inflammasome were identified. In this review, we summarize the recent discoveries made on Yersinia effector proteins and their contribution to Yersinia pathogenesis.

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“…Indeed, Yersinia enterocolitica synthesizes the injected effector YopT ( Yersinia outer protein T) (Shao et al, 2003). YopT is a cysteine protease with an endopeptidase activity that cleaves the C‐terminal part of RhoA, Rac1 and Cdc42, thus severing their lipid anchor (Shao et al, 2003; Fueller and Schmidt, 2008) (Figure 2). This in turn triggers a release of the active form of Rac1 from membranes, resulting in its translocation to the nucleus (Wong and Isberg, 2005).…”

Section: Covalent Modifications Of Rho Gtpases Induced By Cellular Prmentioning

confidence: 99%

Direct modifications of Rho proteins: deconstructing GTPase regulation

Visvikis

Maddugoda

Lemichez

2010

Biology of the Cell

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Small GTPases of the Rho protein family are master regulators of the actin cytoskeleton and are targeted by potent virulence factors of several pathogenic bacteria. Their dysfunctional regulation can lead to severe human pathologies. Both host and bacterial factors can activate or inactivate Rho proteins by direct post-translational modifications: such as deamidation and transglutamination for activation, or ADP-ribosylation, glucosylation, adenylylation and phosphorylation for inactivation. We review and compare these unconventional ways in which both host cells and bacterial pathogens regulate Rho proteins.

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The polybasic region of Rho GTPases defines the cleavage by Yersinia enterocolitica outer protein T (YopT)

Cited by 16 publications

References 28 publications

Bead‐based protein–protein interaction assays for the analysis of Rho GTPase signaling

Bead‐based protein–protein interaction assays for the analysis of Rho GTPase signaling

Yersiniatype III effectors perturb host innate immune responses

Direct modifications of Rho proteins: deconstructing GTPase regulation

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