ライフサイエンスコーパス: acta

1 nd member of the TGF-beta family, activin A (ActA).

2 (PLCs; PlcA and PlcB) and a surface protein (ActA).

3 ated with the Listeria monocytogenes protein ActA.

4 mplex for its upstream activators N-WASP and ActA.

5 in L. monocytogenes by the bacterial protein ActA.

6 d motility mediated by the bacterial protein ActA.

7 ), two phospholipases C (PlcA and PlcB), and ActA.

8 r than drug therapy, as were participants in ACTA.

9 ted with invasion, including InlA, InlB, and ActA.

10 Complete gene sequences for actA (1,929 bp) and inlA (2,235 bp) provided the highest

11 ation in vitro, which is further enhanced by ActA [6] [7].

12 Here we show that activin A (rh-ActA), a known regulator of follicle formation and growt

13 Activin A (ActA), a TGFbeta superfamily member, was secreted from b

14 s on the mlp-actA-plcB operon, which encodes ActA, a bacterial nucleation-promoting factor that media

15 aments, and this capacity can be enhanced by ActA, a protein used by Listeria to polymerize actin.

16 ActA accumulated more efficiently at younger, less inert

17 an intrinsically disordered protein such as ActA across a porous barrier similar to a peptidoglycan

18 e rate of expression increase was changed in actA, actB, actC, or actD mutant strains.

19 A modified model of Nielsen et al. (Acta Agriculturae Scand Section A, 63, 2013 and 126) usi

20 rnatively, with activins, such as Activin A (ActA), ALK2 forms nonsignaling complexes that negatively

21 found to cluster into these three lineages, actA alleles segregated independently.

22 polymorphisms revealed 8 hly, 11 inl4, and 2 actA alleles.

23 Surprisingly, our ActA allelic series enabled us to uncouple L. monocytoge

24 We generated an ActA allelic series within the defined Ena/VASP-binding

25 Expression of the cell surface protein ActA allows L. monocytogenes to activate host actin regu

26 in healthy postmenopausal females, and anti-ActA alone or placebo in healthy males.

27 tested multiple-dose administration of anti-ActA alone or placebo in healthy postmenopausal females,

28 dose administration of anti-GDF8 alone, anti-ActA alone, several dose combinations of anti-GDF8 + ant

29 binary solution containing profilin and the ActA analogue increased the observed rates of intracellu

30 Recent evidence suggests the ActA analogue may act by displacing the profilin-binding

31 ar concentration = 80 nM profilin plus 80 nM ActA analogue).

32 We included 674 eligible participants from ACTA and 814 from AMBITION-cm in the pooled analysis (to

33 The actA and actB null mutations substantially decreased the

34 Relative to ActA and ActB, ActC exhibited lower affinity for the cog

35 ame deletion of actB decreased expression of actA and actE to the same extent.

36 While the biological functions of ActA and activin B (ActB) have been well characterized,

37 ss Cameroon, Malawi, Tanzania, and Zambia in ACTA and eight hospitals across Botswana, Malawi, South

38 We propose that ActA and endogenous WASP family proteins promote Arp2/3-

39 follistatin (FS288) and its complexes (FS288-ActA and FS288-Mstn).

40 Collectively, these results indicate that actA and hly are differentially regulated in response to

41 ter gene system to compare the expression of actA and hly during intracellular growth to that during

42 Transcription of actA and hly, encoding LLO, is regulated by PrfA and inc

43 Several actA and hlyA alleles appeared to be predominantly assoc

44 PPPX(D/E), X = P or T] contained in Listeria ActA and in the p90 host-cell vinculin fragment generate

45 urce, based on the phylogenies inferred from actA and inlA (P = 0.02 and P = 0.07, respectively; Sour

46 actA and inlA also showed evidence of positive selection

47 actA and inlA as well as prs and the hypervariable house

48 sponse gene (sigB), and two virulence genes (actA and inlA) revealed between 11 (gap) and 33 (inlA) a

49 s response gene (sigB), two virulence genes (actA and inlA), and two intergenic regions (hly-mpl and

50 However, quantitative immunoprecipitation of ActA and LLO from infected J774 cells demonstrated appro

51 tion and proteolysis of Lm virulence factors ActA and LLO, thereby promoting phagosome escape and cel

52 utant strain bearing double deletions in the actA and plcB virulence genes for an initial clinical sa

53 The 5' untranslated regions (5' UTRs) of actA and prfA have been shown to upregulate expression o

54 genes requires the bacterial surface protein ActA and protein components present in host cell cytopla

55 nine mutations in the NH2-terminal domain of ActA and replaced the endogenous actA gene with these mo

56 L. monocytogenes primarily involves PlcA and ActA and that either one of these factors must be presen

57 s the actin-nucleating activity of wild-type ActA and the Arp2/3 complex while also reducing the freq

58 differently to nucleation and stimulation by ActA and WASP, whereas p34/p20 bind actin filaments and

59 Both Bcl-2(ActA) and Bcl-2(Cytob5) suppressed p53-mediated transact

60 We investigated the roles of actin (ActA) and fimbrin (FimA) in hyphal growth in Aspergillus

61 allelic analysis of the virulence genes hly, actA, and inlA to uncover linkages between independent p

62 propose a model in which the polarization of ActA, and possibly other Gram-positive cell wall-associa

63 which ActB is activated by the C signal via ActA, and the act operon activates transcription of the

64 against the FEFPPPPTDE sequence of Listeria ActA, and this antibody: (a) localized at the trailing e

65 d not persist into puberty and both adult rh-ActA- and vehicle-treated animals demonstrated normal fe

66 endent on the long repeats and the amount of ActA; and (3) movement rate dependent on the PRRs.

67 ActA appears to control at least four functions that col

68 Furthermore, intracellular induction of actA appears to require additional steps or factors beyo

69 Listeriolysin O (LLO) and ActA are essential virulence determinants for Listeria m

70 the Listeria monocytogenes virulence factor ActA are propelled by actin polymerization.

71 These results suggest that GDF8 and ActA are the dominant negative regulators of muscle mass

72 nhances fibrosis and metastasis, implicating ActA as a potential therapeutic target to inhibit metast

73 erial pole expressing the highest density of ActA as a tail formed.

74 The accumulation of ActA at the bacterial poles displayed slower kinetics, o

75 timulated phosphoprotein (VASP), which binds ActA at the surfaces of Listeria cells and enhances bact

76 ocus sequence typing (MLST) based on loci in actA, betL, hlyA, gyrB, pgm, and recA.

77 e mapped an Mpl-dependent processing site in ActA between amino acid residues 207 to 238.

78 ActA binds Arp2/3 with a K(d) of 0.6 microm and competes

79 Combining GDF8 and ActA blocking antibodies led to greater muscle growth th

80 ActA/BMP chimeras can be useful in the study of receptor

81 comparable with wild type activin A, whereas ActA/BMP2 chimera showed a slightly reduced affinity tow

82 ActA/BMP7 chimera retained Act RII binding affinity comp

83 contribute to the extracellular induction of actA but did not affect intracellular levels of expressi

84 tro binding assays show that SH2-Bbeta binds ActA but not VASP; however, binding to ActA is greater i

85 y be explained by acid-dependent cleavage of ActA by the bacterial metalloprotease, Mpl.

86 costs were derived from costs of FLU+5FC in ACTA, by subtracting 5FC drug and monitoring costs.

87 n polymerization-based motility generated by ActA can be used to move nonbiological cargo, as has bee

88 mulated phosphoprotein (VASP) recruitment by ActA can bypass defects in actin monomer-binding.

89 Genomic regions of actA, cmdA, gapdh, his3 and tef1 were amplified and sequ

90 uss "symmetry breaking" dynamics observed in ActA-coated bead experiments, and the implications of th

91 SH2-Bbeta enhances actin-based movement of ActA-coated beads in a biomimetic actin-based motility a

92 le symmetry breaking previously observed for ActA-coated spherical beads.

93 promoter is located immediately upstream of actA coding sequences, while the second promoter is cont

94 ion, the relative abundance of intracellular ActA compared to that of intracellular LLO is a function

95 The binding of heparin to the FS288-ActA complex was disrupted at 500 mM salt, whereas it wa

96 s, binding of heparin to FS288 and the FS288-ActA complex was enhanced.

97 est binding activity for FS288 and the FS288-ActA complex, whereas smaller heparin molecules could in

98 Challenges of immune mice with actA-deficient and with wild-type recombinant L. monocyt

99 Although mice immunized with low-dose actA-deficient L. monocytogenes had a substantial recall

100 contrast, mice immunized with a low dose of actA-deficient L. monocytogenes had approximately 10-fol

101 High-dose immunization with actA-deficient L. monocytogenes resulted in substantial

102 ty, elicited by immunization with attenuated actA-deficient Listeria monocytogenes, on the CD8(+)-T-c

103 CD8 T cell response following infection with ActA-deficient LM.

104 selectively deleting two virulence factors, ActA (DeltaactA) and Internalin B (DeltainlB), the immun

105 ed version, Advanced Complex Trait Analysis (ACTA), demonstrating dramatically improved performance.

106 The pure complex is sufficient to initiate ActA-dependent actin polymerization at the surface of L.

107 y, we compared the biochemical activities of ActA derivatives with the phenotypes of corresponding mu

108 We have synthesized and characterized an ActA dimer and provide evidence that the two ActA molecu

109 of actin nucleation mimic that of synthetic ActA dimers.

110 te bacterial movement rates both depended on ActA distribution, which in turn was tightly coupled to

111 To directly correlate ActA distributions to actin dynamics and motility of liv

112 etic lineages were confirmed when 22 partial actA DNA sequences were analyzed.

113 ocytogenes mutants expressing high levels of actA during in vitro growth were selected after chemical

114 he observation that L. monocytogenes lacking ActA Ena/VASP-binding sites were up to 400-fold less vir

115 plcB, cotranscribed with actA, encodes a broad-specificity phospholipase C that c

116 stly, a mutant which expressed low levels of ActA exhibited a phenotype indicative of a threshold; th

117 m of PrfA, known as PrfA*, increased overall actA expression in broth-grown cultures of both wild-typ

118 ng mutant isolates displayed a wide range of actA expression levels, and many were less sensitive to

119 ults indicate that the dramatic induction of actA expression that occurs in the host cell cytosol is

120 iptional activation; however, no increase in actA expression was detected following the introduction

121 The intracellular induction of actA expression was found to be dependent upon the actA

122 articipate in the intracellular induction of actA expression, L. monocytogenes mutants expressing hig

123 oter elements have been reported to regulate actA expression.

124 ributions of individual promoter elements to actA expression.

125 mally, a double mutant lacking both PlcA and ActA failed to grow in wild-type macrophages and colocal

126 Interestingly, profilin competes with ActA for binding of Arp2/3, but actophorin (cofilin) doe

127 lthough prior in vivo work has proposed that ActA forms dimers on the surface of L. monocytogenes, di

128 icial lipid vesicles coated with the protein ActA from the bacterial pathogen Listeria monocytogenes

129 ical staining pattern observed with the anti-ActA FS-1 antibody), indicating that motile bacteria att

130 of actin polymerization, (2) polarization of ActA function, (3) transformation of actin polymerizatio

131 sual phenotypes illustrate the complexity of ActA functions that control the actin-based motility of

132 expression of the hly fusion relative to the actA fusion in LB broth.

133 tosol of J774 cells, and the activity of the actA fusion was approximately 3-fold higher than that of

134 ay indicated that the hly fusion but not the actA fusion was significantly activated in Luria-Bertani

135 veral isolates contained mutations affecting actA gene expression that mapped at least 40 kb outside

136 l domain of ActA and replaced the endogenous actA gene with these molecular variants.

137 rized strain of L. monocytogenes lacking the actA gene.

138 pPL1 was used to introduce the hly and actA genes at comK-attBB' in deletion strains derived fr

139 The hly and actA genes were transcriptionally fused to Escherichia c

140 We examined the localization of ActA::GFP and FimA::GFP in live cells, and each displaye

141 In actively growing hyphae, cortical ActA::GFP and FimA::GFP patches were highly mobile throu

142 onocytogenes strain containing a chromosomal actA-gfpuv-plcB transcriptional fusion showed that blood

143 fA-dependent virulence factor PlcA, PlcB, or ActA grew normally, a double mutant lacking both PlcA an

144 n of actin polymerization in vitro, but pure ActA had no effect.

145 of Listeria monocytogenes virulence protein ActA have typically focused on the behavior of bacteria

146 for lung metastasis, as genetic targeting of ActA in breast cancer cells significantly attenuated lun

147 Moreover, high levels of ActA in human patients with breast cancer were associate

148 via ActRIIA/B, as blockade of both GDF8 and ActA in mice/monkeys matches the muscle growth of ActRII

149 Two actA in vitro expression mutants contained novel mutatio

150 or many of the unique physical properties of ActA including its extended structure, aberrant mobility

151 Ena/VASP F-actin-binding region did so in an ActA-independent manner.

152 meric proteins, as in the case of activin A (ActA; InhbetaA/InhbetaA) or activin C (ActC; InhbetaC/In

153 After induction of expression, ActA initially appeared at distinct sites along the side

154 , L. monocytogenes mutants with deletions of actA, inlA, inlB, inlAB, plcA, and plcB resembled their

155 ActA is a bacterially encoded protein that enables Liste

156 We also present observations indicating that ActA is a natively unfolded protein, largely random coil

157 n vitro, the actin monomer-binding region of ActA is critical for stimulating Arp2/3-dependent actin

158 binds ActA but not VASP; however, binding to ActA is greater in the presence of VASP.

159 mal activity at saturating concentrations of ActA is identical to the most active domains of the WASP

160 olar lysis and entry into the cytosol, while ActA is required for bacterial spread to adjacent cells.

161 Previously, we suggested that activin A (ActA) is the key second negative regulator acting via Ac

162 dy, we pooled individual-level data from the ACTA (ISRCTN45035509) and AMBITION-cm (ISRCTN72509687) r

163 coated with a fluid lipid bilayer rendering ActA laterally mobile, beads predominantly migrated with

164 th, and this finding correlated with LLO and ActA levels detectable in broth cultures.

165 time, changes in serum total GDF8 and total ActA levels over time, and the presence of anti-drug ant

166 tion of oligoproline sequences in ActA or an ActA-like host protein to induce host cell actin assembl

167 odel in which proteolysis unmasks vinculin's ActA-like oligoproline sequence.

168 pression of the profibrogenic genes (Col1a1, Acta, Loxl2, and Tgfbeta) (P < 0.001).

169 -drug antibodies against the GDF8 mAb or the ActA mAb.

170 on, pharmacokinetic profiles of the GDF8 and ActA mAbs in serum over time, changes in serum total GDF

171 ion we published previously [Hammond et al., Acta Mater. 144, 561-578 (2018)] for small bubbles, but

172 cells, such as hepatocytes, and the indirect ActA-mediated infection by cell-to-cell spread from adja

173 The Listeria monocytogenes surface protein ActA mediates actin-based motility by interacting with a

174 ActA mediates cross-talk between breast cancer cells and

175 ins of CD2AP fused to Listeria monocytogenes ActA mitochondria-targeting sequence) inhibited REF52 ce

176 ActA dimer and provide evidence that the two ActA molecules do not interact with each other even when

177 the close packing ( approximately 19 nm) of ActA molecules on the surface of L. monocytogenes is so

178 s were transformed into the L. monocytogenes actA mutant DP-L1942.

179 y of the glcV mutant compared to an isogenic actA mutant reference strain was next tested in an exper

180 Surprisingly, Listeria ActA mutant strains lacking the putative phosphoinositid

181 although, in fetal infection, the number of ActA- mutant bacteria was 100-fold lower, compared with

182 The ActA- mutant, which is impaired in cell-to-cell spread a

183 s shared by other immunogenic mutants (e.g., actA mutants), our glcV mutant was tested for vaccine ef

184 hly promoter (h30) or linked in frame to the ActA N-terminal 100 amino acids and driven by the actA p

185 By chemical cross-linking, ActA, N-WASP, and Scar1 contact the same three subunits

186 d oral colonization with one of the mutants, actA-negative (DeltaactA) L. monocytogenes, to restrict

187 ates in cortical tissue (McKee et al., 2016, Acta Neuropathologica, 131, 75-86).

188 roinjection of a peptide matching the second ActA oligoproline repeat (FEFPPPPTDE) stops Listeria loc

189 monocytogenes requires polar distribution of ActA on its surface to move.

190 eltampl strain displayed increased levels of ActA on the bacterial surface in protrusions.

191 207-238 strain displayed increased levels of ActA on the bacterial surface in protrusions.

192 ytosolic mutants revealed that all expressed ActA on their cell surface and formed actin tails with a

193 ASP recognition of oligoproline sequences in ActA or an ActA-like host protein to induce host cell ac

194 the Bnip3 transmembrane domain with that of Acta or cytochrome b(5).

195 pausal females, combination anti-GDF8 + anti-ActA or placebo in healthy postmenopausal females, and a

196 brane domains from the mitochondrial protein ActA or the endoplasmic reticulum protein cytochrome b5.

197 everal dose combinations of anti-GDF8 + anti-ActA, or placebo in healthy postmenopausal females; part

198 Acta, Part B, 2013, 79-80, 63-71) and the C-sigma model

199 been given to the surface environment where ActA performs its pivotal role in bacterial actin-based

200 truction of a transcriptional fusion between actA-plcB and the green fluorescent protein gene of Aequ

201 This dissemination process relies on the mlp-actA-plcB operon, which encodes ActA, a bacterial nuclea

202 stream mpl gene via the generation of an mpl-actA-plcB transcript.

203 ape from host cell vacuoles, did not express actA/plcB at detectable levels within infected tissue cu

204 actA/plcB expression began approximately 30 min postinfe

205 ated the detailed examination of patterns of actA/plcB expression within infected tissue culture cell

206 teria into the host cytoplasm and subsequent actA/plcB expression.

207 We have directly examined the de novo ActA polarization process in vitro by using an ActA-RFP

208 nt with our in vitro observations of de novo ActA polarization.

209 ape, the metalloprotease Mpl is required for ActA processing and protrusion resolution.

210 e InhbetaC chain functions to interfere with ActA production by forming less active ActAC heterodimer

211 interacting peptides and found that, as with ActA, proline-rich sequences were the sole zyxin sequenc

212 eterologous dal gene tightly regulated by an actA-promoted resolvase recombination system.

213 N-terminal 100 amino acids and driven by the actA promoter (a30).

214 The actA promoter is dependent upon a regulatory factor know

215 n broth-grown cultures of both wild-type and actA promoter mutant strains, but the levels of inductio

216 a high-affinity PrfA binding site within the actA promoter.

217 or the activation and binding of PrfA to the actA promoter.

218 The Listeria monocytogenes ActA protein acts as a scaffold to assemble and activate

219 Polystyrene beads coated with purified ActA protein can undergo directional movement in an acti

220 These results indicate that the ActA protein directs at least three separable events: (1

221 The Listeria monocytogenes ActA protein induces actin-based motility by enhancing t

222 The ActA protein is an essential determinant of pathogenicit

223 The ActA protein is responsible for the actin-based movement

224 The Listeria monocytogenes ActA protein mediates actin-based motility by recruiting

225 s coated uniformly with the L. monocytogenes ActA protein migrated equally well in either of two dist

226 The ActA protein of Listeria monocytogenes is an essential v

227 t is similar to the C-terminal domain in the ActA protein of the bacteria, Listeria monocytogenes.

228 ation is associated with polarization of the ActA protein on the fluid vesicle surface, which may rei

229 The polar distribution of the ActA protein on the surface of the Gram-positive intrace

230 Once in the cytosol, the L. monocytogenes ActA protein recruits host cell Arp2/3 complexes and ena

231 factor that promoted the ability of Listeria ActA protein to activate the Arp2/3 complex to trigger a

232 of the variable surface distribution of the ActA protein to initiation and steady-state movement.

233 L. monocytogenes mutants lacking the ActA protein, which is essential for intracellular movem

234 the bacterial cell surface by the listerial ActA protein.

235 oline-rich repeat region of L. monocytogenes ActA protein.

236 xpression was found to be dependent upon the actA proximal promoter; the mpl promoter appeared to con

237 of L. monocytogenes must be due to polarized ActA rather than intrinsic actin network forces.

238 ocytogenes actin nucleation-promoting factor ActA, remain associated with the bacterial membrane but

239 l junction assembly through the VASP-binding ActA repeat region.

240 triction of bacteria lacking PlcA, PlcB, and ActA required FIP200 and TBK1, both involved in the engu

241 The minimal Arp2/3-binding site of ActA (residues 144-170) is C-terminal to both actin-bind

242 Here we show that two domains of ActA (residues 85-104 and 121-138) with sequence similar

243 in O (LLO) and ActA, the products of hly and actA, respectively, to establish a productive intracellu

244 and 38 alleles were identified for hlyA and actA, respectively.

245 Importantly, introduction of exogenous rh-ActA revealed an intrinsic ovarian quorum sensing mechan

246 Modeling of ALK2:ActA reveals that binding relies on ActA's fingertip reg

247 tA polarization process in vitro by using an ActA-RFP (red fluorescent protein) fusion.

248 actA, ribC, and purM demonstrated the highest levels of

249 of ALK2:ActA reveals that binding relies on ActA's fingertip region, mirroring the interaction of Ac

250 ActA signaling was functionally important for lung metas

251 complexes that negatively regulate ALK2 and ActA signaling.

252 d suggest that the actin-binding sequence of ActA spans 40 amino acids.

253 ActA spans both the bacterial membrane and the peptidogl

254 These data suggest that ActA stimulates the Arp2/3 complex by both VASP-dependen

255 isteria monocytogenes requires the bacterial ActA surface protein and the host cell Arp2/3 complex.

256 The Listeria surface protein ActA synergises with recruited host proteins to induce a

257 wever, when combined, the Arp2/3 complex and ActA synergistically stimulated the nucleation of actin

258 strated approximately 70-fold more cytosolic ActA than cytosolic LLO.

259 ther, while the lower level of production of ActA than of LLO in broth can be accounted for by transc

260 a peptide derived from the Listeria protein ActA that undergoes a random coil to helix transition up

261 gy, several genes were identified, including actA, that exhibited such an expression profile.

262 cytogenes requires listeriolysin O (LLO) and ActA, the products of hly and actA, respectively, to est

263 actA, the protein product of which is required for cell-

264 in lacks the oligoproline sequences found in ActA, the surface protein required for locomotion of the

265 All act genes, actA to actE, are expressed together and constitute an o

266 tosol, WT L. monocytogenes utilized PLCs and ActA to avoid subsequent xenophagy.

267 erimentally validate our model and show that ActA translocation depends on the cell-envelope dimensio

268 ent with the empirical data, the k(A) for rh-ActA-treated was twice that of vehicle-treated animals.

269 day 19 were also derived for vehicle and rh-ActA treatment conditions.

270 The ACTA trial demonstrated that, compared with 2 weeks of a

271 In the ACTA trial, 1-week (short course) amphotericin B plus fl

272 ryptococcal Meningitis Treatment for Africa (ACTA) trial, 2 weeks of fluconazole (FLU) plus flucytosi

273 ActA upregulated the expression of profibrotic factors i

274 the tightly bound bacterial surface protein ActA uses its multiple oligoproline registers [consensus

275 ctin dynamics and motility of live bacteria, ActA was fused to a monomeric red fluorescent protein (m

276 n comparison to induction in broth cultures, actA was highly induced (226-fold) and hly was moderatel

277 ong V-armed members, GDF8 was latent whereas ActA was not.

278 rene beads coated with the bacterial protein ActA, we have systematically varied a series of biophysi

279 Data in ACTA were collected between Feb 12, 2013, and Jan 10, 20

280 iveness and costs of FLU+5FC were taken from ACTA, which included a costing analysis at the Zambian s

281 The expression of actA, whose protein product is required for L. monocytog

282 ngertip region, mirroring the interaction of ActA with its other receptor, ALK4.