ライフサイエンスコーパス: RhoGAP

1 RhoGAP also appears to function by stabilizing several r

2 Defects resulting from loss of CYK-4 RhoGAP activity can be rescued by activating mutations i

3 Consistent with CYK-4 RhoGAP activity contributing to GEF activation, the cata

4 Thus, counterintuitively, CYK-4 RhoGAP activity promotes RhoA activation.

5 We suggest that ZEN-4/MKLP1 and CYK-4/RhoGAP regulate an early step in epithelial polarization

6 Centralspindlin kinesin-6/RhoGAP complex, a midbody component critical for both th

7 -phosphatase domain followed by an ASH and a RhoGAP-like domain.

8 results demonstrate that YopE functions as a RhoGAP to downregulate multiple Rho GTPases, leading to

9 ild type p190 appeared able to function as a RhoGAP.

10 family member c-ten requires R474 to bind a RhoGAP called DLC-1 (deleted in liver cancer).

11 The N-terminal domain comprises a RhoGAP activity, while the C-terminal domain comprises a

12 -activating proteins (GAPs), which contain a RhoGAP domain equipped with a characteristic arginine fi

13 otein 1 (MKLP1), and CYK-4, which contains a RhoGAP (GTPase-activating protein) domain.

14 er cancer 1) tumor suppressor gene encodes a RhoGAP protein that inactivates Rho GTPases, which are i

15 Now the generation of mice deficient for a RhoGAP suggests that this small G protein might also reg

16 of the genes identified in this screen is a RhoGAP protein, SH3-domain binding protein 1 (SH3BP1).

17 Depletion of myosin-IXA, a RhoGAP and actin motor protein, in collectively migratin

18 her DBL family Rho GEFs, Rho effectors, or a RhoGAP.

19 contributes to DLC1 tumor suppression via a RhoGAP-independent mechanism, and suggest that DLC1 inac

20 idomain protein with a RhoGTPase-activating (RhoGAP) domain and a StAR-related lipid transfer (START)

21 trameric complex consisting of kinesin-6 and RhoGAP (Rho-family GTPase-activating protein) subunits,

22 n cooperation between its tensin binding and RhoGAP activities, although neither activity depends on

23 EF (guanine nucleotide exchange factors) and RhoGAP (GTPase activating proteins), proteins that contr

24 otein RhoA complexed with MgF3(-) , GDP, and RhoGAP, which has the mutation Arg85'Ala.

25 e protein did inhibit both the intrinsic and RhoGAP-stimulated GTP hydrolysis rates of Cdc42 and Rac1

26 reveal that the binding sites for IQGAP1 and RhoGAP on the small G proteins overlap only partially.

27 gh multiple cellular targets for the PRR and RhoGAP have been identified, and their functions delinea

28 a-5 genes, encoding homologues of RhoGEF and RhoGAP, respectively, as regulators of axon regeneration

29 f the ongoing combined actions of RhoGEF and RhoGAP.

30 view, we focus on the ability of RhoGEFs and RhoGAPs to form complexes with diverse binding partners,

31 , Ses1 and Ses2, which interact with the ASH-RhoGAP-like (ASPM-SPD-2-Hydin homology and Rho-GTPase Ac

32 ed by the same missense mutations in the ASH-RhoGAP-like domain that also disrupt APPL1 binding.

33 allographic studies reveal a role of the ASH-RhoGAP-like domains in positioning the phosphatase domai

34 ion with APPL1, which is mediated by the ASH-RhoGAP-like domains of OCRL and is abolished by disease

35 recruitment of actomyosin and the associated RhoGAP Myo9b.

36 P190-B RhoGAP (p190-B, also known as ARHGAP5) has been shown to

37 he tyrosine-phosphorylation status of p190-B RhoGAP and its resulting subcellular relocalization.

38 trate-trapping mutants, we identified p190-B RhoGAP as a SHP-2 substrate.

39 ." Cells derived from embryos lacking p190-B RhoGAP exhibit excessive Rho activity, are defective for

40 When dephosphorylated, p190-B RhoGAP has been shown to stimulate the activation of Rho

41 ly inactive mutant of SHP-2 inhibited p190-B RhoGAP tyrosyl dephosphorylation, RhoA activity, and myo

42 During myogenesis, p190-B RhoGAP was tyrosyl dephosphorylated concomitant with the

43 e lacking the Rho-inhibitory protein, p190-B RhoGAP, are 30% reduced in size and exhibit developmenta

44 hat the Rho GTPase and its regulator, p190-B RhoGAP, are components of a critical switch in the adipo

45 y suggest that SHP-2 dephosphorylates p190-B RhoGAP, leading to the activation of RhoA.

46 In p190-B RhoGAP-deficient mice, CREB phosphorylation is substanti

47 we show that a signalling network of p190-B RhoGAP-ROS-TGF-beta-p38(MAPK) balances HSPC self-renewal

48 es, further suggesting a link between p190-B-RhoGAP and non-canonical TGF-beta signalling in HSPC dif

49 ant negative mutants of Cdc42 and Rac and by RhoGAP p190.

50 inger resembles the one within the canonical RhoGAP domains and inserts into the nucleotide-binding p

51 0RhoGAP (herein referred to as CRAD; catenin-RhoGAP association domain).

52 rmodynamic data pertaining to the Rac1/Cdc42-RhoGAP complexes.

53 n we identify "cold spots" in the Rac1/Cdc42-RhoGAP/IQGAP1 interfaces.

54 In addition to a conserved RhoGAP domain at the N terminus, multiple proline-rich m

55 f RGA-3/4, which functions as a conventional RhoGAP for RhoA.

56 which are predicted to encode three distinct RhoGAPs that share only the GAP domain.

57 Thus, distinct RhoGAPs, encoded by the same gene, regulate different ma

58 on occurred at mRNA level and relied on DLC1 RhoGAP function, leading to suppression of high level of

59 Hence, p120 associates with the DLC1 RhoGAP domain by targeting the catalytic arginine finger

60 on mode of the p120 SH3 domain with the DLC1 RhoGAP domain that is atypical and does not follow the c

61 the serines, located N-terminal to the DLC1 RhoGAP domain, induces strong binding of that N-terminal

62 RhoA were increased upon depletion of either RhoGAP.

63 p190B mutant exhibits dramatically enhanced RhoGAP activity, consistent with a model whereby binding

64 SNX26, a brain-enriched RhoGAP, plays a key role in dendritic arborization durin

65 functions as a molecular mimic of eukaryotic RhoGAPs to inactivate Rho GTPases through RhoGDI.

66 Green fluorescent protein-RhoGDI and ExoS RhoGAP cooperatively stimulated actin reorganization and

67 ane inhibited the actions of RhoGDI and ExoS RhoGAP on the translocation of Cdc42 from membrane to cy

68 RhoA in vivo, the relationship between ExoS RhoGAP and the eukaryotic regulators of Rho GTPases is n

69 ation of actin cytoskeleton mediated by ExoS RhoGAP.

70 skeleton elicited by type III-delivered ExoS RhoGAP.

71 This indicates that ExoS RhoGAP and RhoGDI function in series to inactivate Rho G

72 n actin reorganization, suggesting that ExoS RhoGAP functions as a molecular mimic of eukaryotic RhoG

73 Although the ExoS RhoGAP inactivates Cdc42, Rac, and RhoA in vivo, the rel

74 Although ExoT RhoGAP stimulates actin reorganization through the inact

75 onal interaction between RhoA and individual RhoGAP which involves distinct structural determinants o

76 nd structurally and show that they influence RhoGAP activity.

77 y competitively and very potently inhibiting RhoGAP activity.

78 ons as an autoinhibitory domain of intrinsic RhoGAP activity.

79 ulation of neurite outgrowth by exerting its RhoGAP activity and that its cellular activity may be re

80 vealed an allosteric regulation site for its RhoGAP activity.

81 regulation of neurite outgrowth through its RhoGAP activity.

82 screening Rho GTPase regulators, myosin-IXA RhoGAP was identified as a key requirement for cell-cell

83 p68RacGAP, a novel Vezf1-interacting 68-kDa RhoGAP domain-containing protein.

84 luding original data from a double-knockdown RhoGAP genetic screen, which likely reflects the redunda

85 is regulated by the asymmetrically localized RhoGAP Deleted in liver cancer (DLC1) in the cytoplasm a

86 of Myo9b (Myo9b-RhoGAP), a unique motorized RhoGAP that specifically targets RhoA for controlling ce

87 ntracellular domain interacts with the Myo9b RhoGAP domain and inhibits its activity; therefore, SLIT

88 missing in the RhoGAP domain of Myo9b (Myo9b-RhoGAP), a unique motorized RhoGAP that specifically tar

89 ers impaired the catalytic activity of Myo9b-RhoGAP and affected the Myo9b-mediated cell migration.

90 Here, we determined the structure of Myo9b-RhoGAP in complex with GDP-bound RhoA and magnesium fluo

91 Our data indicate that Myo9b-RhoGAP accelerates RhoA GTP hydrolysis by a previously u

92 Unexpectedly, Myo9b-RhoGAP contains two arginine fingers at its catalytic si

93 m, which may be shared by other noncanonical RhoGAP domains lacking the auxiliary asparagine.

94 A novel RhoGAP family member, p200RhoGAP, is cloned in human and

95 he conservation of the catalytic activity of RhoGAP (Rho-specific GAP) on the 6-TGTP-Rac1 adduct to p

96 ion to activation of RhoGEF(s), reduction of RhoGAP (p190) is a critical mechanism by which increased

97 ented by knowledge of the basic structure of RhoGAP/GTPase signaling, namely, that GAPs act directly

98 reflects the redundant network structure of RhoGAP/GTPase signaling.

99 xplain why, unique among the large family of RhoGAPs, p190A exhibits a significantly increased mutati

100 method makes mediocre predictions using only RhoGAP single-knockdown morphological data, yet achieves

101 h a large set of other representative SH3 or RhoGAP proteins.

102 Centralspindlin's own RhoGAP domain also contributes to furrow ingression.

103 p115 RhoGAP directly binds PRL-1 in vitro and in cells via it

104 l interaction between the SH3 domain of p115 RhoGAP and MEKK1 and results in activation of ERK1/2.

105 by inhibiting the catalytic activity of p115 RhoGAP.

106 hin the PxxP ligand-binding site of the p115 RhoGAP SH3 domain occupies a folded groove within PRL-1.

107 sults demonstrate that PRL-1 binding to p115 RhoGAP provides a coordinated mechanism underlying ERK1/

108 amino acids, has 86% homology with rat p122 RhoGAP gene, and was localized by fluorescence in situ h

109 P190 RhoGAP (GTPase activating protein) is a potent Rho regul

110 p190 RhoGAP is a 190-kDa protein that stably associates with

111 p190 RhoGAP, a GTPase regulatory protein, provides this coord

112 hesion molecules, the action of PKC and p190 RhoGAP leads to a modulation of Rho GTPase activity to d

113 The minimal regions of Syx and p190 RhoGAP that bind Rnd3 are not sequence-related but have

114 or in response to integrin engagement, p190 RhoGAP is rapidly translocated to regions of membrane ru

115 ates excessively, suggesting a role for p190 RhoGAP in the regulation of +Rho-mediated actin assembly

116 Mice lacking functional p190 RhoGAP exhibit several defects in neural development tha

117 phila using RNA interference identified p190 RhoGAP as essential for axon stability in mushroom body

118 Here we identify p190 RhoGAP (p190), the most abundant GAP for RhoA in cells,

119 ng Rac1 activation and RhoA inhibition, p190 RhoGAP is critical to the protective effects of Ang-1 ag

120 cells of the neural tube floor plate of p190 RhoGAP mutant mice, polymerized actin accumulates excess

121 ltinucleation phenotype is dependent on p190 RhoGAP activity, determine that the N-terminal GBDS1 reg

122 ion with their effectors such as Syx or p190 RhoGAP.

123 ng, the tyrosine phosphorylated protein p190 RhoGAP becomes associated with GRB2 in LA significantly

124 tor p190 Rho-GTPase-activating protein (p190 RhoGAP) also play an important regulatory role in fear m

125 ility effects of endotoxin but requires p190 RhoGAP to do so.

126 a FRET biosensor, we further show that p190 RhoGAP and RhoA act downstream of the PAR-6/aPKC complex

127 Herein, we report that p190 RhoGAP forms a high-affinity complex with Rho GTPases in

128 kinase C (PKC), and we have found that p190 RhoGAP is also a PKC substrate in vivo.

129 We have determined that p190 RhoGAP is specifically expressed at high levels througho

130 FII-I as a specific interactor with the p190 RhoGAP FF domains.

131 Inhibition of the p190 RhoGAP-downstream kinase ROCK in LA during fear conditio

132 Thus, the p190 RhoGAP/ROCK pathway, which regulates the morphology of d

133 revealed that RAFTK is associated with p190 RhoGAP (p190), RasGAP and ErbB-2, and plays an essential

134 s an abundant SH2-mediated complex with p190 RhoGAP in cells expressing activated tyrosine kinases.

135 Treatment with p190 RhoGAP small interfering RNA completely abolishes the ab

136 Our results identify p190 RhoGAPs as effectors of Rnd proteins and demonstrate a n

137 n the context of cell migration are the p190 RhoGAPs (p190A and p190B), which function to modulate Rh

138 The p190 RhoGAPs undergo complex regulation, including phosphoryl

139 ivating protein for Rho family members (p190(RhoGAP); p190) and membrane-protrusive activities at inv

140 ative regulator of Rho family GTPases, p190A RhoGAP, is one of six mammalian proteins harboring so-ca

141 We identify p190A RhoGAP as a major target for ERK signaling in adhesion a

142 phosphorylation leads to inhibition of p190A RhoGAP activity in vitro and in vivo.

143 equired for the negative regulation of p190A RhoGAP activity.

144 itional regulatory mechanism unique to p190A RhoGAP that involves priming-dependent phosphorylation b

145 ted that IQGAP1 binds to both RhoA and p190A-RhoGAP, a GTPase-activating protein that normally inhibi

146 P1 acts as a scaffold that colocalizes p190A-RhoGAP and RhoA, inactivating RhoA and suppressing airwa

147 al sections revealed colocalization of p190A-RhoGAP and RhoA; however, these proteins did not colocal

148 ing of Rac1 relieves autoinhibition of p190B RhoGAP function.

149 p200 RhoGAP co-localizes with p120 RasGAP in cells and forms

150 p200 RhoGAP, a member of the Rho GTPase-activating protein (R

151 The morphology of the foci induced by p200 RhoGAP is distinct from that formed by Rac or Rho activa

152 uppresses the foci formation induced by p200 RhoGAP, suggesting that the Ras-ERK pathway is required

153 hat the Ras-ERK pathway is required for p200 RhoGAP-mediated cell transformation.

154 vity of the N-terminal RhoGAP domain in p200 RhoGAP is also required for its full transforming activi

155 region and the Src homology 3 domain of p200 RhoGAP and p120 RasGAP, respectively.

156 Expression of p200 RhoGAP results in a significant increase of Ras-GTP and

157 Here we show that ectopic expression of p200 RhoGAP stimulates fibroblast cell proliferation and cell

158 Mutations of p200 RhoGAP that disrupt interaction with p120 RasGAP abolish

159 he GDP- and GTP-bound states suppresses p200 RhoGAP transformation.

160 proliferation and provide evidence that p200 RhoGAP can mediate cross-talks between Ras- and Rho-regu

161 genic Ras, raising the possibility that p200 RhoGAP may engage Ras signaling.

162 ransferase, or the GTPase-activating protein RhoGAP p190 causes a marked reduction in the number of p

163 orms allowing Rho-GTPase-activating protein (RhoGAP) activity to be focused at a definite locus.

164 th N-terminal Rho GTPase-activating protein (RhoGAP) and C-terminal ADP-ribosyltransferase domains.

165 C-1 encodes a Rho GTPase-activating protein (RhoGAP) and negative regulator of specific Rho family pr

166 suppressor, a Rho GTPase-activating protein (RhoGAP) associated with focal adhesions.

167 1 (DLC-1) is a RhoGTPase-activating protein (RhoGAP) domain containing tumor suppressor that is often

168 9 include the Rho GTPase-activating protein (RhoGAP) domain, and residues 234-453 include the 14-3-3-

169 member of the Rho GTPase-activating protein (RhoGAP) family, was previously implicated in the regulat

170 , which encodes a GTPase activating protein (RhoGAP) for the RhoA and RhoC small GTPases.

171 e analyses of Rho GTPase activating protein (RhoGAP) function in Drosophila using RNA interference id

172 of the Rho family GTPase-activating protein (RhoGAP) MgcRacGAP/CYK-4 and the kinesin MKLP1/ZEN-4, is

173 codes a novel Rho GTPase-activating protein (RhoGAP) required for restricting the ROP1 activity to th

174 ene encodes a Rho GTPase-activating protein (RhoGAP) that functions as a tumor suppressor in several

175 BPGAP1 is a Rho GTPase-activating protein (RhoGAP) that regulates cell morphogenesis, cell migratio

176 ctly to p190B Rho GTPase-activating protein (RhoGAP), a major modulator of Rho signaling.

177 guanosine triphosphatase activating protein (RhoGAP), PAC-1, which mediates C. elegans radial polarit

178 pression of a Rho GTPase-activating protein (RhoGAP), RhoGAP7/DLC-1, via activation of the transcript

179 values of the Rho GTPase-activating protein (RhoGAP)-catalyzed reactions were significantly increased

180 by Rho-selective GTPase-activating proteins (RhoGAP), which have generally been presumed to act as tu

181 The Rho GTPase-activating proteins (RhoGAPs) are a family of multifunctional molecules that

182 eins known as RhoGTPase Activating Proteins (RhoGAPs) that catalyse the conversion of RhoGTPases to t

183 C1-3) encode Rho-GTPase-activating proteins (RhoGAPs) whose expression is frequently down-regulated o

184 y inhibiting Rho GTPase activating proteins (RhoGAPs).

185 ode Rho-specific GTPase-activating proteins (RhoGAPs).

186 ted action of its proline-rich region (PRR), RhoGAP domain, and the BNIP-2 and Cdc42GAP homology (BCH

187 The number of potential Rac/RhoGAPs largely exceeds the number of Rac/Rho GTPases an

188 in other species, namely, mouse HSPE71, Rat RhoGAP protein, S cerevisiae leucyl tRNA synthetase and

189 Deletion of these domains reduces RhoGAP activity.

190 Our findings suggest that the REN1 RhoGAP controls a negative-feedback-based global inhibit

191 roliferation and that this function requires RhoGAP activity.

192 LC1 binding to S100A10 did not affect DLC1's RhoGAP activity, but it decreased the steady-state level

193 criptome revealed high expression of several RhoGAP genes in BLBC tumors, raising the possibility tha

194 We describe a brain-specific RhoGAP splice variant, BARGIN (BGIN), which comprises a

195 (DLC1), which encodes a protein with strong RhoGAP (GTPase activating protein) activity and weak Cdc

196 nteraction with p190B, modulates subcellular RhoGAP localization and activity, thereby providing a no

197 s a regulatory element for its COOH-terminal RhoGAP domain.

198 ti-internalization factor with an N-terminal RhoGAP domain and a C-terminal ADP-ribosyltransferase do

199 ingly, the RhoGAP activity of the N-terminal RhoGAP domain in p200 RhoGAP is also required for its fu

200 cal drivers of BLBC growth, and propose that RhoGAPs can act as oncogenes in cancer.

201 The RhoGAP activity is required for full DLC-dependent tumor

202 The RhoGAP activity, which is required for full DLC-dependen

203 The RhoGAP domain of p200RhoGAP stimulated the GTPase activi

204 The RhoGAP domains of Bcr and 3BP-1, which were thought to b

205 interaction between recombinant RhoA and the RhoGAP domains of p190, p50RhoGAP, Bcr, and 3BP-1.

206 utations in the 5-phosphatase domain and the RhoGAP-like domain.

207 aracterisation reveals that cv-c encodes the RhoGAP protein RhoGAP88C.

208 rface and a clathrin box protruding from the RhoGAP-like domain.

209 ed a set of chimeric molecules by fusing the RhoGAP domain of p190, a GTPase-activating protein that

210 ential for inhibiting tumor cell growth, the RhoGAP activities were significantly reduced in these mu

211 ses in both worm and fly have identified the RhoGAP-like protein Syd-1 as a key positive regulator of

212 , the auxiliary asparagine is missing in the RhoGAP domain of Myo9b (Myo9b-RhoGAP), a unique motorize

213 SH3 domain of p120 selectively inhibits the RhoGAP activity of all three DLC isoforms as compared wi

214 Interestingly, the RhoGAP activity of the N-terminal RhoGAP domain in p200

215 e motility defect of macrophages lacking the RhoGAP (Rho GTPase-activating protein) myosin IXb (Myo9b

216 Transient expression of the RhoGAP domain and the full-length molecule, but not the

217 Expression of the RhoGAP domain of p200RhoGAP in Swiss 3T3 fibroblasts inh

218 o actin filaments, whereas expression of the RhoGAP domain partially rescued the cell scattering phen

219 he characterization of a novel member of the RhoGAP family, Rga8, identified from a two-hybrid screen

220 tein 1, Rasip1, and its binding partner, the RhoGAP Arhgap29.

221 stretch of polybasic residues preceding the RhoGAP domain regulates CdGAP activity in vivo and is re

222 a small polybasic region (PBR) preceding the RhoGAP domain that mediates specific binding to negative

223 Consistent with the fact that the RhoGAP activity of DLC-1 is essential for inhibiting tum

224 Structural analyses revealed that the RhoGAP domain of Myo9b contains a unique patch that spec

225 We show that the RhoGAP PAC-1/ARHGAP21 inhibits CDC-42 activity at AJs, a

226 A new study reports that the RhoGAP SPV-1 senses membrane curvature and cell stretch

227 ong binding of that N-terminal region to the RhoGAP domain, converting DLC1 from an open, active dime

228 omeric state, Rac1 became insensitive to the RhoGAP stimulation, albeit maintaining the responsivenes

229 DLC-1 is a multi-domain protein, with the RhoGAP catalytic domain flanked by an amino-terminal ste

230 es with the interaction of RhoA-GTP with the RhoGAP domain, reduces the hydrolysis of RhoA-GTP, the b

231 this, we examined the roles of two of these RhoGAPs, ArhGAP11A (also known as MP-GAP) and RacGAP1 (a

232 gical data from genetic screens, apply it to RhoGAP/GTPase regulation in Drosophila, and evaluate its

233 e a built-in arginine finger, in addition to RhoGAPs, for negative regulation.

234 monstrate that Moe interacts with an unusual RhoGAP, Conundrum (Conu), and recruits it to the cell co

235 we have developed a novel strategy utilizing RhoGAP-Rho chimeras to specifically down-regulate indivi

236 iological activity, as did a mutant that was RhoGAP-deficient.

237 ng both bound nucleotide and Mg(2+), whereas RhoGAP utilizes the Mg(2+) cofactor to achieve high cata

238 h RhoGAPArg85'Ala relative to wild-type (WT) RhoGAP.

239 troduction of the Y. pseudotuberculosis YopE RhoGAP protein could be bypassed by the overproduction o