ライフサイエンスコーパス: ExoS

1 ExoS (453 amino acids) is a bi-functional type III cytot

2 ExoS (453 amino acids) is a bi-functional type-III cytot

3 ExoS (453 amino acids) is a bifunctional type III cytoto

4 ExoS ADP-ribosylated recombinant moesin at a linear velo

5 ExoS ADP-ribosylates Ras and prevents it from interactin

6 ExoS ADP-ribosylation of Rac1 is cell line dependent.

7 ExoS and ExoT are closely related bifunctional proteins

8 ExoS did not ADP-ribosylate Crk-I.

9 ExoS includes both GTPase-activating (GAP) and ADP-ribos

10 ExoS is a bifunctional protein having both GTPase-activa

11 ExoS is a bifunctional Type III cytotoxin of Pseudomonas

12 ExoS is a bifunctional type III cytotoxin produced by Ps

13 ExoS is a bifunctional type III cytotoxin secreted by Ps

14 ExoS is a bifunctional type III cytotoxin that is secret

15 ExoS is bifunctional, with an amino-terminal RhoGAP and

16 ExoS structural gene sequence comparisons found the gene

17 ExoS(E381D), a mutant deficient in ADP-ribosyltransferas

18 ExoS, ExoT, ExoY, and ExoU all possess enzymatic activit

19 ExoS/ChvI also has important roles in regulating succino

20 1 or with a specific JNK inhibitor abolishes ExoS-triggered apoptosis, demonstrating the requirement

21 , a 14-3-3 family protein, factor-activating ExoS (FAS) had no influence on the activity of the GAP d

22 o acids 234-453) encodes a factor-activating ExoS-dependent ADP-ribosyltransferase activity.

23 Pseudomonas aeruginosa ExoS is a bifunctional type III cytotoxin.

24 Pseudomonas aeruginosa ExoS is a bifunctional type III-secreted cytotoxin.

25 Pseudomonas aeruginosa ExoS is a type III-secreted type III-secreted, bifunctio

26 ur known effector proteins of P. aeruginosa (ExoS, ExoT, ExoU, and ExoY) in wax moth killing.

27 idues outside the ADPRT region are affecting ExoS ADPRT activity.

28 c cells, and 11 of 33 had antibodies against ExoS, while most CF sera contained antibodies against Po

29 An ExoS(1-107)-green fluorescent protein (GFP) fusion prote

30 the entry and alignment of P. aeruginosa and ExoS along actin filaments.

31 ) visualize the ability of P. aeruginosa and ExoS to align with actin filaments, and (v) demonstrate

32 Type III-delivered ExoS(DeltaMLD) and ExoS showed similar capacities for eliciting a cytotoxic

33 gest that periplasmically localized ExoR and ExoS-ChvI function together in a unique and critical reg

34 Bacterial-associated ExoS and ExoS that had been secreted by P. aeruginosa also showed

35 Invasive P. aeruginosa secrete ExoT and ExoS, but exsA mutation has little impact on their short

36 cretion of type 3 exotoxins (ExoU, ExoT, and ExoS).

37 Since ExoU and ExoS are usually not secreted by the same strain, it has

38 adherence, type III secretion induction, and ExoS translocation.

39 wed that serum antibodies to PopB, PcrV, and ExoS were common.

40 type III secretion proteins (PopD, PcrV, and ExoS) and a flagellum-associated protein (FliD).

41 ndicating that ExoR negatively regulates and ExoS-ChvI positively regulates downstream genes.

42 Green fluorescent protein-RhoGDI and ExoS RhoGAP cooperatively stimulated actin reorganizatio

43 membrane inhibited the actions of RhoGDI and ExoS RhoGAP on the translocation of Cdc42 from membrane

44 The activities of these toxins, and ExoS specifically, on the permeability properties of pol

45 Bacterial-associated ExoS and ExoS that had been secreted by P. aeruginosa al

46 rescent energy transfer was detected between ExoS and 14-3-3 proteins but not between ExoS and Rabs p

47 een ExoS and 14-3-3 proteins but not between ExoS and Rabs proteins.

48 , and RhoA in vivo, the relationship between ExoS RhoGAP and the eukaryotic regulators of Rho GTPases

49 gulator ExoR interacts genetically with both ExoS and ChvI, and localizes to the periplasm of S. meli

50 xplain the increase in active Rac1 caused by ExoS ADPRT activity.

51 ion of Ras from the cytotoxicity elicited by ExoS.

52 ribosylation of soybean trypsin inhibitor by ExoS.

53 ibution in human airway cells intoxicated by ExoS, -T, and -Y.

54 biological contributions to intoxications by ExoS.

55 ganization of actin cytoskeleton mediated by ExoS RhoGAP.

56 observed for the ADP-ribosylation of Ras by ExoS, where ADP-ribosylated Ras loses the ability to bin

57 The modification of these residues by ExoS would be predicted to interfere with Rac1 inactivat

58 ase subfamily that can be ADP ribosylated by ExoS and indicates that ExoS can inhibit both Ras and Ra

59 anslocated ExoS and that ADP-ribosylation by ExoS affects RalA interaction with its downstream effect

60 nd in vitro, whereas the ADP-ribosylation by ExoS is poly-substrate-specific and includes Ras as an e

61 udied the effect of Rab5 ADP-ribosylation by ExoS on its cellular function, i.e., regulation of early

62 n contributes to in vivo ADP-ribosylation by ExoS.

63 ly diminished after Rab5 ADP-ribosylation by ExoS.

64 is indicates that within the mammalian cells ExoS undergoes a negatively charged modification, in add

65 nsferase activity, and in J744-Eclone cells, ExoS ADP-ribosyltransferase activity caused a more sever

66 tor proteins injected into eukaryotic cells, ExoS and ExoU are cytotoxic.

67 since the expression of the ADPRT-competent ExoS also induced rapid cell death in the Drosophila mel

68 Further, the CT694 MLD is able to complement ExoS DeltaMLD when ectopically expressed.

69 In contrast, ExoS was secreted by 16 (46%) of the 35 examined isolate

70 xotoxin A (ETA) and the type III cytotoxins (ExoS, ExoT, ExoU, and ExoY).

71 -lactone quorum sensing signal and decreased ExoS/T production respectively.

72 Type III delivered ExoS ADP-ribosylated moesin and ezrin (and/or radixin) i

73 ns as observed for native type-III delivered ExoS.

74 Type III-delivered ExoS co-immunoprecipitated 14-3-3 proteins and Rab9, Rab

75 of substrates modified by type III-delivered ExoS identified a 70-kDa protein as an early and predomi

76 Type III-delivered ExoS localized to both plasma membrane and perinuclear r

77 ese results indicate that type III-delivered ExoS localizes on the host endosomes and utilizes multip

78 cytoskeleton elicited by type III-delivered ExoS RhoGAP.

79 eukaryotic cells, whereas type III-delivered ExoS was membrane associated.

80 Type III-delivered ExoS(DeltaMLD) and ExoS showed similar capacities for el

81 Type III-delivered ExoS(DeltaMLD) localized within the cytosol of eukaryoti

82 Although type III-delivered ExoS(DeltaMLD) stimulated the reorganization of the acti

83 ons in the type III secretion (T3S) effector ExoS to manipulate P. aeruginosa infection, and (iii) hi

84 we determined which of the three effectors (ExoS, ExoT, or ExoY) were required for bleb niche format

85 ne of the major type III secreted effectors, ExoS, prevented triggering of type III secretion by bact

86 One of these effectors, ExoS, ADP-ribosylates several host cell proteins, includ

87 By expressing an EGFP-ExoS fusion protein, we were able to directly correlate

88 y leading to apoptosis, but also establishes ExoS as a valuable tool, in principle, for the elucidati

89 (c20) does not function directly in the ExoR-ExoS/ChvI regulatory pathway and that ExoR(m) is the fun

90 e on the activity of the GAP domain of ExoS (ExoS-GAP).

91 h isogenic mutants secreting wild-type ExoS, ExoS defective in GTPase-activating protein (GAP) activi

92 e type III secretion system effectors (ExoU, ExoS, and PcrV) and for strain relatedness using randoml

93 biochemical and enzymatic functions of ExoU, ExoS, and ExoT, three effector proteins secreted by this

94 cterial strain that naturally secretes ExoU, ExoS, and ExoT were generated to carefully evaluate the

95 ruginosa strain PAO1 or PAK, which expresses ExoS, ExoT, and ExoY, but not ExoU.

96 Infection with P. aeruginosa expressing ExoS lacking both GAP and ADPRT activities resulted in t

97 oculture of P. aeruginosa strains expressing ExoS with HL-60 myeloid cells revealed the cell line to

98 GST-CpA co-immunoprecipitation studies found ExoS ADP-ribosylation of CpA to efficiently inhibit CpA

99 dy provides insight into a mechanism for how ExoS ADP-ribosylation of Rab5 inhibits Rab5 function.

100 ts provide insight into the mechanism of how ExoS/ChvI regulates its downstream targets and lay a fou

101 There is limited information on how ExoS or other type III cytotoxins enter and target intra

102 ing to ExoS and cause a dramatic increase in ExoS/ChvI-dependent gene expression.

103 e pathogenesis of P. aeruginosa keratitis in ExoS- and ExoT-producing strains is almost entirely due

104 ant negative Rab5(Ser34Asn) does not inhibit ExoS trafficking to the perinuclear region of intoxicate

105 S in the periplasm of S. meliloti to inhibit ExoS/ChvI activity, and that ExoR represents a novel per

106 eLa cells with the presence of intracellular ExoS and further proved the dependence of this process o

107 eb niches and intracellular survival involve ExoS ADP-r activity and implicate a connection between b

108 NAD and FAS, the GAP activity of full-length ExoS was reduced about 10-fold, whereas NAD and FAS did

109 The YopE-MLD localized ExoS to intracellular membranes and targeted ExoS to ADP

110 calization domain (residues 51-72) localizes ExoS to a perinuclear region within eukaryotic cells.

111 The Sinorhizobium meliloti ExoS/ChvI two-component signaling pathway is required fo

112 In S. meliloti, ExoS/ChvI is a key regulator of gene expression for exop

113 tion immunofluorescent microscopy to monitor ExoS translocation.

114 P-ribosylation by wild-type and E381A mutant ExoS by two-dimensional electrophoresis found the former

115 Using [(32)P]NAD, ExoS-GAP was identified as a substrate of the ADP-ribosy

116 o ExoS-producing Pa, but not an isogenic non-ExoS producing strain.

117 led that auto-ADP-ribosylation of Arg-146 of ExoS was crucial for inhibition of GAP activity in vitro

118 Residues 51-72 of ExoS (termed the membrane localization domain, MLD) were

119 ucine-rich motif within residues 51 to 77 of ExoS.

120 ted study not only highlights the ability of ExoS ADPRT to modulate host cell signaling, eventually l

121 n into HeLa cells but limited the ability of ExoS to ADP-ribosylate Ras GTPases.

122 delivery into HeLa cells, or the ability of ExoS to ADP-ribosylate Ras GTPases.

123 to cytoskeleton dynamics, and the ability of ExoS to ADP-ribosylate the ERM proteins links ADP-ribosy

124 xpression of Rab5(EF) rescued the ability of ExoS to inhibit intracellular trafficking.

125 n of Rab5(TL) does not affect the ability of ExoS to modify intracellular trafficking, while expressi

126 he coordinate function of both activities of ExoS in J774A.1 macrophages was assessed by using P. aer

127 Alternatively, the ADPRT activity of ExoS altered cellular adherence and morphology and was l

128 l ADP-ribosyltransferase (ADPRT) activity of ExoS have been found to target but exert opposite effect

129 ether the ADP-ribosyltransferase activity of ExoS influences its GAP activity.

130 hough the ADP-ribosyltransferase activity of ExoS is dependent upon FAS, a 14-3-3 family protein, fac

131 The ADPRT activity of ExoS targeted Ras and RalA but not Rab or Rho proteins,

132 e ADP-ribosyltransferase (ADP-r) activity of ExoS, but not the Rho-GAP activity nor the membrane loca

133 te of the ADP-ribosyltransferase activity of ExoS.

134 not required to observe the pI conformers of ExoS; it enhanced the resolution and formation of pI con

135 r studies also highlight the contribution of ExoS to the opportunistic nature of P. aeruginosa infect

136 The mechanism of cytotoxicity of ExoS is unclear.

137 S from P. aeruginosa or type III delivery of ExoS into eukaryotic cells.

138 fluence on the activity of the GAP domain of ExoS (ExoS-GAP).

139 were examined between the Rho GAP domain of ExoS and Rho GTPases in CHO cells.

140 Coexpression of the Rho GAP domain of ExoS changed the intracellular distribution of GFP-Rac a

141 Coexpression of the Rho GAP domain of ExoS did not change the distribution of GFP-Rho, which w

142 sociated with the ADP-ribosylating domain of ExoS, as bacteria expressing plasmids lacking expression

143 While the Rho GAP domains of ExoS and YopE share structural homology, unlike ExoS, th

144 Examination of the effect of ExoS ADP-ribosylation on CpA function found a moderate (

145 GST pull-down assays identified an effect of ExoS ADPRT activity on RalA activation.

146 as required for the antiphagocytic effect of ExoS and was linked to interference of lamellopodium and

147 y translocated ExoS, indicating an effect of ExoS on cellular RalA function.

148 ate the mechanisms underlying the effects of ExoS GAP and ADPRT activities on P. aeruginosa internali

149 erential targeting and coordinate effects of ExoS GAP and ADPRT activity on Rac1 within the host cell

150 S ADPRT activity was required for effects of ExoS on DNA synthesis and long-term cell rounding.

151 e ADP-ribosylation and functional effects of ExoS on RalA, ExoS was found to ADP-ribosylate endogenou

152 domains on Rac1 function, limited effects of ExoS-GAP on Rac1 inactivation were evident in HT-29 cell

153 line to be resistant to the toxic effects of ExoS.

154 dies provide insight into the enhancement of ExoS ADPRT activity within the eukaryotic cell microenvi

155 study, we demonstrate that the expression of ExoS in HeLa cells by eukaryotic expression vector effec

156 ved, which is required for the expression of ExoS/ChvI-regulated symbiosis genes, we characterized wi

157 GTPase-activating protein-deficient form of ExoS rounded cells, indicating the ADP-ribosyltransferas

158 The pI heterogeneity of ExoS was independent of a mass change and thus represent

159 The importance of ExoS/ChvI signalling in microbe-host interactions is und

160 Inactivation of ExoS ADPRT activity resulted in significantly enhanced T

161 Inactivation of ExoS GAP activity allowed P. aeruginosa to be internaliz

162 Significantly higher levels of ExoS ADP-ribosyltransferase (ADPRT) activity were detect

163 Plasma membrane localization of ExoS was transient and had a half-life of approximately

164 The cellular mechanism of ExoS GAP activity included an inactivation of Rac1 funct

165 ors across the host cell plasma membrane) of ExoS is indeed self-regulated and that this inhibition o

166 ganization of the leucines within the MLD of ExoS is different from that of previously described leuc

167 with a fusion protein containing the MLD of ExoS.

168 or the membrane localization domain (MLD) of ExoS, was required to elicit this phenotype.

169 e studies confirm the bifunctional nature of ExoS activity within macrophages when translocated by TT

170 f cell lysates with Mn(2+) shifted the pI of ExoS(E381D) to a pI identical to secreted ExoS.

171 he ADP-ribosyltransferase (ADPRT) portion of ExoS include low molecular weight G-proteins (LMWG-prote

172 s reflected both the increased production of ExoS and the production of ExoS having a higher specific

173 sed production of ExoS and the production of ExoS having a higher specific activity.

174 substitutions occurring within the region of ExoS encoding GAP function.

175 the ADP ribosyltransferase (ADPR) regions of ExoS or ExoT also impaired proapoptotic activity in infe

176 actions is underscored by the requirement of ExoS/ChvI orthologues for virulence of the related alpha

177 To reveal the auto-ADP-ribosylation of ExoS in intact cells, tetanolysin was used to produce po

178 se studies draw attention to the key role of ExoS ADPRT activity in causing the effects of bacteriall

179 leb niche formation and the known role(s) of ExoS-mediated apoptosis and/or Rab GTPase inactivation.

180 he MLD did not inhibit type III secretion of ExoS from P. aeruginosa or type III delivery of ExoS int

181 atest impact on virulence while secretion of ExoS had an intermediate effect and ExoT had a minor eff

182 Secretion of ExoS or ExoY, 2 other proteins transported by this syste

183 tified arginine 55 and 69 of CpA as sites of ExoS ADP-ribosylation.

184 f Rac1 were identified as preferred sites of ExoS ADP-ribosylation.

185 To focus our study of ExoS/ChvI transcriptional target genes, we performed tra

186 To understand how ExoR suppression of ExoS is relieved, which is required for the expression o

187 ve proteolysis to relieve its suppression of ExoS.

188 tand the cellular basis for the targeting of ExoS ADPRT activity to Rac1, an inverse relationship was

189 lectively represent high affinity targets of ExoS.

190 Bacterial translocation of ExoS into epithelial cells is associated with diverse ef

191 activity demonstrated that the virulence of ExoS was largely dependent on its ADP-ribosyltransferase

192 Inactivation of Rab5 was dependent on ExoS ADP-ribosyltransferase activity, and in J744-Eclone

193 GTPase-activating protein (GAP) activity, or ExoS defective in ADP-ribosyltransferase activity demons

194 pressing and translocating wild-type ExoS or ExoS defective in GAP and/or ADPRT activity.

195 commonly found combinations of ExoU/ExoT or ExoS/ExoT provides redundant and failsafe mechanisms to

196 o detected were antibodies to ExoS, ExoU, or ExoS and ExoU, the latter indicating sequential P. aerug

197 In strain PAK, ExoS is the major cytotoxin required for colonization an

198 the first detection of antibodies to pooled ExoS/PopB occurred at a time similar to those of detecti

199 ruginosa mutant strain that fails to produce ExoS did not lead to any change in HRP uptake.

200 case of P. aeruginosa, the effector protein ExoS is central to limiting effector injection.

201 PRT) activity of a type III secreted protein ExoS.

202 xpression of the type III secretory proteins ExoS, ExoT, ExoU, or PcrV.

203 ing two type III secreted effector proteins, ExoS and ExoT.

204 Two of the four translocated proteins, ExoS and ExoU, are cytotoxic to cells during infection a

205 tion and functional effects of ExoS on RalA, ExoS was found to ADP-ribosylate endogenous RalA and rec

206 Microinjection of recombinant ExoS into Xenopus oocytes induced strong inhibition of b

207 this association is important for regulating ExoS/ChvI signalling.

208 Sinorhizobium meliloti requires ExoS/ChvI two-component signalling to establish a nitrog

209 of the host innate immune response requires ExoS-mediated ADP-ribosylation of Ras in neutrophils.

210 s for the type III secretion system restored ExoS secretion but did not always reestablish cytotoxici

211 Auto-ADP-ribosylated ExoS analyzed from eukaryotic cells displayed pI heterog

212 in was determined to be auto-ADP-ribosylated ExoS, whereas the 25-kDa protein appeared to represent a

213 xoS but more basic than auto-ADP-ribosylated ExoS.

214 ophages, where Rac1 was not ADP-ribosylated, ExoS caused a decrease in the levels of active Rac1, and

215 Pseudomonas aeruginosa exoenzyme S (ExoS) ADP-ribosylates multiple eukaryotic targets to pro

216 Exoenzyme S (ExoS) is a bifunctional Pa TTS effector protein, with GT

217 Exoenzyme S (ExoS) is a bifunctional toxin directly translocated into

218 Pseudomonas aeruginosa Exoenzyme S (ExoS) is a bifunctional type-III cytotoxin.

219 Exoenzyme S (ExoS) is a bifunctional virulence factor directly transl

220 Pseudomonas aeruginosa exoenzyme S (ExoS) is a type III secretion (TTS) effector, which incl

221 Pseudomonas aeruginosa exoenzyme S (ExoS) is an ADP-ribosyltransferase that modifies low-mol

222 Exoenzyme S (ExoS) is translocated into eukaryotic cells by the type

223 Type III-delivered exoenzyme S (ExoS) preferentially ADP-ribosylated membrane-associated

224 ur different effector proteins, exoenzyme S (ExoS), ExoT, ExoU, and ExoY.

225 P. aeruginosa to be internalized and secrete ExoS within T24 cells, but as with wild-type ExoS, trans

226 d to a more acidic pI than type III secreted ExoS but more basic than auto-ADP-ribosylated ExoS.

227 of ExoS(E381D) to a pI identical to secreted ExoS.

228 it was proposed that P. aeruginosa secreting ExoS, upon infection, shuts down host cell survival sign

229 with nearly all of these isolates secreting ExoS and ExoT but not ExoU.

230 In this study, ExoS is shown to be capable of ADP-ribosylating 6 candid

231 ) alone or together with exoenzymes S and T (ExoS/T/Y) generated the most virulent amyloids.

232 ExoS to intracellular membranes and targeted ExoS to ADP-ribosylate small molecular weight membrane p

233 studies showed that the N-terminus targeted ExoS to intracellular membranes within eukaryotic cells.

234 membrane localization domain [MLD]) targets ExoS to the Golgi-endoplasmic reticulum (Golgi-ER) of ma

235 udes a novel leucine-rich motif that targets ExoS to the perinuclear region of cultured cells.

236 ane localization domain (MLD), which targets ExoS to perinuclear vesicles within mammalian cells.

237 ExoU is over 100-fold more cytotoxic than ExoS.

238 more severe inhibition of phagocytosis than ExoS Rho GTPase activity.

239 on and T3S translocation, (iii) confirm that ExoS ADPRT activity targeted a cellular substrate that i

240 noninvasive PA103 strains demonstrated that ExoS or ExoT that is injected into host cells by a type

241 These comparisons found that ExoS was translocated more efficiently in TPA-differenti

242 ts with an exoS96::Tn5 mutant indicated that ExoS/ChvI influences the expression of a few hundred gen

243 e ADP ribosylated by ExoS and indicates that ExoS can inhibit both Ras and Rap signaling pathways in

244 This indicates that ExoS RhoGAP and RhoGDI function in series to inactivate

245 T activity-dependent manner, indicating that ExoS alone is sufficient to trigger apoptotic death of h

246 Recent studies observed that ExoS is auto-ADP-ribosylated upon delivery into eukaryot

247 In this study, we report that ExoS ADP ribosylates Rap1b at Arg41 and that ADP ribosyl

248 An E381A ADPRT mutation revealed that ExoS ADPRT activity was required for effects of ExoS on

249 Previous studies showed that ExoS ADP ribosylated Ras at Arg41 which interfered with

250 Immunofluorescence experiments showed that ExoS colocalized with Rab9, Rab6, and Rab5.

251 In a previous study, we showed that ExoS of P. aeruginosa, when injected into host cells thr

252 GDI on actin reorganization, suggesting that ExoS RhoGAP functions as a molecular mimic of eukaryotic

253 Our results support that ExoS ADP-ribosylates and affects the function of the cyt

254 ts conclusively show for the first time that ExoS is a virulence factor.

255 Although the ExoS RhoGAP inactivates Cdc42, Rac, and RhoA in vivo, th

256 s suggest that both the ExoR protein and the ExoS/ChvI two-component regulatory system are involved i

257 at the YopE MLD functionally complements the ExoS MLD for intracellular targeting in mammalian cells.

258 train PA14 lacks the coding sequence for the ExoS effector protein and does not seem to express ExoY.

259 The cellular pathway responsible for the ExoS-induced cytotoxicity appears to be well conserved,

260 ExoR has been proposed to inhibit the ExoS sensor through direct interaction in the periplasm.

261 xpressing plasmids lacking expression of the ExoS GAP activity nonetheless increased the permeation o

262 Here, we show that injection of the ExoS into HeLa cells activates c-Jun NH(2)-terminal kina

263 D and FAS did not affect the activity of the ExoS-GAP fragment.

264 genes through a mechanism that requires the ExoS/ChvI two-component system.

265 We also show that the ExoS-dependent two-component system suppresses motility

266 on of succinoglycan and flagella through the ExoS/ChvI two-component regulatory system.

267 Therefore, ExoS has opposing effects on different cellular pathways

268 n addition, also detected were antibodies to ExoS, ExoU, or ExoS and ExoU, the latter indicating sequ

269 epeat region of ExoR that disrupt binding to ExoS and cause a dramatic increase in ExoS/ChvI-dependen

270 her, our results indicate that ExoR binds to ExoS in the periplasm of S. meliloti to inhibit ExoS/Chv

271 Mep72 was found to bind directly to ExoS and PcrV and to affect the processing of these prot

272 an epithelial cells that had been exposed to ExoS-producing Pa, but not an isogenic non-ExoS producin

273 ream genes respond directly or indirectly to ExoS/ChvI regulation.

274 active Rac1, and this decrease was linked to ExoS-GAP.

275 te (TPA) rendered the cell line sensitive to ExoS.

276 Similar to ExoS, ExoT and ExoY, ExoU requires either a eukaryotic-s

277 One of the most commonly expressed toxins, ExoS, has two domains that are predicted to affect cytos

278 ed by P. aeruginosa strains that translocate ExoS having GAP or ADPRT mutations allowed the independe

279 llular substrate of bacterially translocated ExoS and that ADP-ribosylation by ExoS affects RalA inte

280 sing the effects of bacterially translocated ExoS on DNA synthesis and cell rounding.

281 1, was inhibited by bacterially translocated ExoS, indicating an effect of ExoS on cellular RalA func

282 nown cellular substrates of TTS-translocated ExoS (TTS-ExoS) ADPRT activity include proteins in the R

283 cells, where Rac1 is ADP-ribosylated by TTS-ExoS, Rac1 was activated and relocalized to the membrane

284 lar substrates of TTS-translocated ExoS (TTS-ExoS) ADPRT activity include proteins in the Ras superfa

285 sylation of a non-G-protein substrate of TTS-ExoS, cyclophilin A (CpA), a peptidyl-prolyl isomerase (

286 rains expressing and translocating wild-type ExoS or ExoS defective in GAP and/or ADPRT activity.

287 and P. aeruginosa cells expressing wild-type ExoS preferentially bound to the leading edge of T24 cel

288 on with isogenic mutants secreting wild-type ExoS, ExoS defective in GTPase-activating protein (GAP)

289 ExoS within T24 cells, but as with wild-type ExoS, translocation was limited in association with disr

290 auto-ADP-ribosylation observed for wild-type ExoS.

291 S and YopE share structural homology, unlike ExoS, the intracellular localization of YopE within mamm

292 Using ExoS-GAP and ADPRT mutants to examine the coordinate eff

293 Collectively, in using ExoS mutants to modulate and visualize T3S translocation

294 In vitro, ExoS is a Rho GAP for Rho, Rac, and Cdc42; however, the

295 ound to the leading edge of T24 cells, where ExoS altered leading-edge architecture and actin anchori

296 sma membrane and perinuclear region, whereas ExoS(DeltaMLD) was localized to the cytosol.

297 ith the cytoskeletal changes associated with ExoS intoxication.

298 we show that ExoR physically associates with ExoS and that this association is important for regulati

299 NLRC4(-/-) mouse corneas were infected with ExoS/T- or ExoU-expressing Pseudomonas aeruginosa.

300 we have found that physical interaction with ExoS stabilizes the ExoR protein.