ライフサイエンスコーパス: RhoGEF

1 RhoGEFs activate small molecular weight GTPases at the p

2 RhoGEFs are central controllers of small G-proteins in c

3 RhoGEFs promote formation of the active GTP-bound state

4 an RhoGEFs with RGS domains, PSD-95/Dlg/ZO-1-RhoGEF and leukemia-associated RhoGEF.

5 esults proved conservation of the G alpha 12-RhoGEF pathway in C. elegans.

6 upting any component of the S1pr2/Galpha(13)/RhoGEF pathway impairs endoderm convergence during segme

7 trate for the first time that the Galpha(13)/RhoGEF-dependent pathway functions downstream of S1pr2 t

8 Thus, the G alpha 12/13-RhoGEF pathway is likely to be involved in embryonic dev

9 WD40, protein kinase, Src homology 2 and 3, RhoGEF, and pleckstrin homology domains involved in cell

10 Caenorhabditis elegans UNC-73 RhoGEF isoforms function in axon guidance, cell migratio

11 CV-mediated signaling defects, rescue unc-73 RhoGEF-2 and rab-2 lethargic movement phenotypes.

12 temporal and spatial requirements of UNC-73 RhoGEF-2 isoform function in mutant rescue experiments.

13 Together, these data suggest UNC-73 RhoGEF-2 isoforms are required for proper neurotransmitt

14 ent with peptidergic neuron function, unc-73 RhoGEF-2 mutants exhibit a decreased level of neuropepti

15 Although unc-73 RhoGEF-2 mutants have grossly normal synaptic morphology

16 The UNC-73E RhoGEF-2 isoform is activated by the G-protein subunit G

17 small interfering RNA against ARHGEF1 and a RhoGEF inhibitor prevented the effects of TGF-beta on Rh

18 Fgd1 contains a RhoGEF domain specific for Cdc42.

19 ing Guanine Nucleotide Exchange Factor) is a RhoGEF of unknown function.

20 vergence of many ASD-related genes.Trio is a RhoGEF protein that promotes actin polymerization and is

21 Ect2 is a RhoGEF that plays a well-established role in formation o

22 eletion of the active site of the obscurin A RhoGEF domain in order to examine its functions in zebra

23 Light-mediated recruitment of a RhoGEF domain to the plasma membrane leads to rapid indu

24 rotein sequence contains in its C-terminus a RhoGEF domain followed by a pleckstrin domain.

25 2 to regulate myocardial migration through a RhoGEF-dependent pathway.

26 ng actin cytoskeleton organization through a RhoGEF/Rho-dependent pathway.

27 n dynamics, Rho GTPases and their activators RhoGEFs are implicated in various aspects of neuronal di

28 n, are dependent upon a catalytically active RhoGEF domain.

29 oguanosine diphosphate (6-TGDP)-Rac1 adduct, RhoGEF (Rho-specific GEF) cannot exchange the 6-TGDP add

30 sequential activation of Galpha(q)/alpha13, RhoGEF, and RhoA, and involve Rho kinase-mediated phosph

31 lyR beta subunit (GLRB), gephyrin (GPHN) and RhoGEF collybistin (ARHGEF9).

32 T is associated with increased p63RhoGEF and RhoGEF-H1 protein expression, increased GEF-H1 activity,

33 ts provide in vivo evidence that the Ras and RhoGEF domains of Sos are separable signaling modules an

34 Its N-terminus, central region and RhoGEF/pleckstrin domain are homologous to the recently

35 However, deletion of RhoGEF or SH3 and RhoGEF domains did not result in any phenotypic changes,

36 Leukemia-associated RhoGEF (LARG) belongs to a small subfamily of RhoGEFs th

37 y of RGS-RhoGEFs p115 or leukemia-associated RhoGEF (LARG) by Galpha13 has previously been demonstrat

38 that oligomerization of leukemia-associated RhoGEF (LARG) functions to prevent nucleocytoplasmic shu

39 leotide exchange factor (leukemia-associated RhoGEF (LARG)) in human head and neck squamous carcinoma

40 Here we show that leukemia-associated RhoGEF (LARG), a RhoA-specific RGS-RhoGEF, is required f

41 activation: PDZ-RhoGEF, leukemia-associated RhoGEF (LARG), and p115RhoGEF.

42 hoA GEFs, PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), link bombesin receptors to RhoA in a non-

43 s (GEFs), PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), use their PDZ domains to bind class B ple

44 lyzed the interaction of leukemia-associated RhoGEF (LARG), which also contains RGS domain, with Galp

45 es cell motility through leukemia-associated RhoGEF (LARG)-dependent Rho GTPase activation.

46 des PDZ-RhoGEF (PRG) and leukemia-associated RhoGEF (LARG).

47 de exchange factor (GEF) leukemia-associated RhoGEF (LARG)/RhoA pathway in skin homeostasis.

48 y of both p115RhoGEF and leukemia-associated RhoGEF but not PDZ-RhoGEF.

49 but not of PDZ RhoGEF or leukemia-associated RhoGEF in human aortic smooth muscle cells (HASMCs).

50 ors p115RhoGEF and LARG (leukemia-associated RhoGEF), fails to stimulate Rho-dependent transcriptiona

51 in-containing RhoGEF and leukemia-associated RhoGEF), RGS3 and RGS12, spinophilin and neurabin-1, SRC

52 s (RhoGEFs) (p115RhoGEF, leukemia-associated RhoGEF, and PDZ-RhoGEF) contain an RH domain and are spe

53 ponses to p115RhoGEF and leukemia-associated RhoGEF.

54 D-95/Dlg/ZO-1-RhoGEF and leukemia-associated RhoGEF.

55 at Ser-70, while only mutants unable to bind RhoGEFs also decreased cellular levels of Bcl-2.

56 previously been shown to interact with both RhoGEF (guanine nucleotide exchange factors) and RhoGAP

57 of direct and independent activation of both RhoGEFs as well as their co-recruitment due to heterodim

58 an-cultured blood vessels, we show that both RhoGEFs are activated by the physiologically and pathoph

59 RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and leukemia-associated RhoGEF), RGS3 and RGS12,

60 of an essential role for the RGS-containing RhoGEF family in signaling to Rho by Galpha12/13-coupled

61 G protein signaling (RGS) domain-containing RhoGEFs (RGS-RhoGEFs) that link activated heterotrimeric

62 We hypothesized that RGS domain-containing RhoGEFs, especially LARG, participate in linking GPCR to

63 13 proteins via RH (RGS homology) containing RhoGEFs.

64 RGS-containing RhoGEFs (RGS-RhoGEFs) represent a direct link between th

65 blasts defective in all three RGS-containing RhoGEFs.

66 that the most active form of the cytokinetic RhoGEF involves complex formation between ECT-2, central

67 In this review, we summarize the role of Dbl RhoGEFs in development and disease, with a focus on Ect2

68 Silencing (siRNA) CD44, EphA2, PATJ, or Dbs (RhoGEF) expression blocked LMW-HA-mediated angiogenesis

69 that LARG is a novel and temporally distinct RhoGEF required for completion of abscission.

70 al. (2016) reveal how acute effects of DOCK6 RhoGEF depletion on RAC1 and CDC42 activation are revers

71 Here, we report that Kalirin9, a dual RhoGEF, binds p75 directly and regulates p75-Nogo recept

72 Pase reflects the very specific role of each RhoGEF in controlling distinct signaling mechanisms invo

73 eterotrimers, indicating that these effector RhoGEFs can engage Galpha13.R7-RGS complexes.

74 hoGEF domain that are predicted to eliminate RhoGEF activity inhibit RhoA activation.

75 functions of its RhoGTPase Exchange Factor (RhoGEF) domain have not been characterized.

76 specific guanine nucleotide exchange factor (RhoGEF) domain that is retained within p210 Bcr-Abl.

77 the Rho guanine nucleotide exchange factor (RhoGEF) Ect2 to the central spindle, abolishes RhoA GTPa

78 specific guanine nucleotide exchange factor (RhoGEF) that regulates neurotrophin-3-induced cell migra

79 The Rho guanine nucleotide exchange factor (RhoGEF) Trio promotes actin polymerization by directly a

80 specific guanine nucleotide exchange factor (RhoGEF) with in vitro exchange activity specific for Rho

81 ning Rho guanine nucleotide exchange factor (RhoGEF), has been studied primarily in tissue culture, w

82 RH) Rho guanine nucleotide exchange factors (RhoGEFs) (p115RhoGEF, leukemia-associated RhoGEF, and PD

83 Rho guanine-nucleotide exchange factors (RhoGEFs) activate Rho GTPases, and thereby regulate cyto

84 ify Rho guanine nucleotide exchange factors (RhoGEFs) activated during cardiac pressure overload in v

85 ily Rho guanine nucleotide exchange factors (RhoGEFs) can serve as the direct downstream effectors of

86 pecific guanine nucleotide exchange factors (RhoGEFs) PDZ-RhoGEF and LARG that stimulate the GDP-GTP

87 and Rho guanine nucleotide exchange factors (RhoGEFs) related to Trio, in a strikingly similar fashio

88 by Rho guanine nucleotide exchange factors (RhoGEFs), a family of proteins involved in the activatio

89 e activated by Rho guanine exchange factors (RhoGEFs), but the RhoGEF(s) required for LTP also remain

90 mily of guanine nucleotide exchange factors (RhoGEFs), which includes PDZ-RhoGEF (PRG) and leukemia-a

91 ous Rho guanine nucleotide exchange factors (RhoGEFs).

92 family guanine nucleotide exchange factors (RhoGEFs).

93 the Rho guanine nucleotide exchange factors (RhoGEFs).

94 ly of RhoGEFs is comprised of the Dbl family RhoGEFs with 70 human members.

95 Here we show that the protein Farp1 [FERM, RhoGEF (ARHGEF), and pleckstrin domain protein 1], a Rac

96 metaphase furrows, a function distinct from RhoGEF/Pebble and likely due to the absence of a RacGAP5

97 ss to separate the role of microtubules from RhoGEF activation.

98 G alpha12Q229L variants uncoupled from RhoGEFs (but not fully functional activated G alpha12Q22

99 Mutations in human FYVE, RhoGEF, and PH domain-containing 1 (FGD1) cause faciogen

100 a new endothelial specific gene named FYVE, RhoGEF, and PH domain-containing 5 (FGD5) that plays a c

101 There are three Rho-specific GEFs (RhoGEFs) in vascular smooth muscle that contain a bindin

102 ulator of G protein signaling (RGS)-homology-RhoGEFs (PDZ domain-containing RhoGEF and leukemia-assoc

103 There are at least 22 human RhoGEFs that contain SH3 domains, raising the possibilit

104 stiffening to Xlfc, a previously identified RhoGEF, which binds microtubules and regulates the actom

105 e findings reveal a dual role for Galphaq in RhoGEF activation, as it both recruits and allostericall

106 RhoGEF(619) to the plasma membrane increases RhoGEF activity towards RhoA, but full activation requir

107 During cytokinesis, RhoA is activated by its RhoGEF, ECT2.

108 t splice form of the multifunctional Kalirin RhoGEF, includes a PDZ [postsynaptic density-95 (PSD-95)

109 ch in PRG-PH that is conserved among all Lbc RhoGEFs.

110 nlike the zygotic, central spindle-localized RhoGEF (Pebble), RhoGEF2 localizes to metaphase furrows,

111 The catalytic activity of membrane-localized RhoGEFs is not dependent on activated Galpha13.

112 ckstrin homology region similar to mammalian RhoGEFs with RGS domains, PSD-95/Dlg/ZO-1-RhoGEF and leu

113 Like many RhoGEF family members, the in vivo exchange activity of

114 of the importance of the obscurin A-mediated RhoGEF signaling in vertebrate organogenesis and highlig

115 e "Ras-binding domain." Syx is a multidomain RhoGEF that participates in early zebrafish development.

116 he utilization of this mechanism by multiple RhoGEFs suggests that this regulatory paradigm may be a

117 is requires the concerted effort of multiple RhoGEFs.

118 Thus, a novel RhoGEF(Pbl)-dependent input promotes the simultaneous as

119 s because of the ongoing combined actions of RhoGEF and RhoGAP.

120 a indicate that in addition to activation of RhoGEF(s), reduction of RhoGAP (p190) is a critical mech

121 However, deletion of RhoGEF or SH3 and RhoGEF domains did not result in any p

122 gf-1 and rga-5 genes, encoding homologues of RhoGEF and RhoGAP, respectively, as regulators of axon r

123 nd PH could play a key role in regulation of RhoGEF activity in vivo.

124 In this review, we focus on the ability of RhoGEFs and RhoGAPs to form complexes with diverse bindi

125 show that the recruitment and activation of RhoGEFs is the cause of a significant time lag between t

126 d are sufficient to modulate the activity of RhoGEFs by hormones via mediating their localization to

127 gical roles of this RGS-containing family of RhoGEFs in vivo.

128 The largest family of RhoGEFs is comprised of the Dbl family RhoGEFs with 70 h

129 is predicted to exist in a broader family of RhoGEFs that includes p115-RhoGEF, Lbc, Lfc, Net1, and X

130 even members of the homologous Lbc family of RhoGEFs which includes the RH-RhoGEFs.

131 s of the poorly characterized DOCK family of RhoGEFs, we performed gene expression profiling of fluor

132 l activation of the RGL-containing family of RhoGEFs.

133 be a common feature in the broader family of RhoGEFs.

134 isolated rat bronchioles, and inhibitors of RhoGEFs (Y16) and Rho-kinase (Y27632), but not the SrcFK

135 bling the well-known activation mechanism of RhoGEFs activated by Galpha12/13.

136 The multitude of RhoGEFs that activate a single Rho GTPase reflects the v

137 through Galpha12 and that the regulation of RhoGEFs by heterotrimeric G proteins G1213 is further mo

138 hoGEF (LARG) belongs to a small subfamily of RhoGEFs that are RhoA-selective and directly activated b

139 that PDZ-RhoGEF, a member of a subfamily of RhoGEFs that contain regulator of G protein signaling do

140 be conserved throughout the Lbc subfamily of RhoGEFs.

141 ion that is integral to the formation of one RhoGEF array.

142 atory mechanism that is likely used by other RhoGEF family members.

143 In contrast to studies of other RhoGEFs, particularly Ect2 and GEF-H1, LARG depletion do

144 lpha12-dependent Pyk2-mediated Gab1 and p115 RhoGEF interactions, leading to Rac1- and RhoA-targeted

145 sine phosphorylation of Pyk2, Gab1, and p115 RhoGEF, leading to Rac1- and RhoA-dependent Pak2 activat

146 PI3K-mediated activation of GEF-H1 and p115 RhoGEF.

147 12 negated thrombin-induced Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, and Pak2 activation, leading to atte

148 ombin-induced activation of Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, and Pak2, resulting in diminished TH

149 inhibition or depletion of Pyk2, Gab1, p115 RhoGEF, Rac1, RhoA, or Pak2 levels substantially attenua

150 In Galphaq, p115 RhoGEF, and RhoA-depleted human umbilical vein ECs, thro

151 i/o-Fyn signaling mediates MCP1-induced p115 RhoGEF and Rac1 GTPase activation.

152 servations, balloon injury (BI) induced p115 RhoGEF tyrosine phosphorylation in rat common carotid ar

153 Moreover, p115 RhoGEF inhibition suppressed MCP1-induced HASMC migratio

154 CP1 induced tyrosine phosphorylation of p115 RhoGEF but not of PDZ RhoGEF or leukemia-associated RhoG

155 Furthermore, depletion of p115 RhoGEF levels also abrogated MCP1- or BI-induced Rac1-NF

156 Src family kinases in the regulation of p115 RhoGEF.

157 n cells surrounding a dying cell target p115 RhoGEF to the actin cortex to control where contraction

158 n neighboring cells reorient and target p115 RhoGEF to this site.

159 These findings suggest that p115 RhoGEF is critical for MCP1-induced HASMC migration and

160 1/CDK6 and upstream of CDK4-PAK1 in the p115 RhoGEF-Rac1-NFATc1-cyclin D1-CDK6-PKN1-CDK4-PAK1 signali

161 eam to Pyk2, Gab1 formed a complex with p115 RhoGEF involving their pleckstrin homology domains.

162 ciation with nucleotide exchange factor p115-RhoGEF, and myosin light chain phosphorylation, which wa

163 broader family of RhoGEFs that includes p115-RhoGEF, Lbc, Lfc, Net1, and Xpln, and identify regions w

164 G), leukemia-associated Rho GEF (LARG), p115-RhoGEF (p115), lymphoid blast crisis (Lbc), and Dbl.

165 Lsc/p115-RhoGEF is a Rho-specific GEF required for normal B and T

166 its essential role in lymphocytes, Lsc/p115-RhoGEF signaling in vivo is not well understood.

167 To define Lsc/p115-RhoGEF signaling pathways in vivo, we set out to identif

168 Expression of dominant negative p115-RhoGEF or p115RhoGEF-specific siRNA inhibited both RhoA

169 Although the GEF activity of p115-RhoGEF (p115), an RGS-RhoGEF, can be stimulated by Galph

170 family of Rho guanine exchange factors, PDZ RhoGEF, which, together with LARG and p115RhoGEF, links

171 action results in the phosphorylation of PDZ RhoGEF and abolishes its ability to mediate the accumula

172 hosphorylation of p115 RhoGEF but not of PDZ RhoGEF or leukemia-associated RhoGEF in human aortic smo

173 PDZ-RhoGEF and LARG can also be phosphorylated by tyrosine k

174 PDZ-RhoGEF exists in cells as a dimer, raising the possibili

175 PDZ-RhoGEF is a member of the regulator family of G protein

176 PDZ-RhoGEF, LARG, and p115RhoGEF are members of a newly iden

177 PDZ-RhoGEF-deficient mice were protected from diet-induced o

178 Interestingly, while characterizing a PDZ-RhoGEF antiserum, we found that a transfected PDZ-RhoGEF

179 t focal adhesion kinase, which activates PDZ-RhoGEF and LARG, is required for bombesin-stimulated Rho

180 ble of linking GPCRs to RhoA activation: PDZ-RhoGEF, leukemia-associated RhoGEF (LARG), and p115RhoGE

181 specific interaction between plexin and PDZ-RhoGEF and to signaling by plexin in the cell.

182 We find that G12/13 and PDZ-RhoGEF are required for entotic invasion, which is drive

183 5RhoGEF, leukemia-associated RhoGEF, and PDZ-RhoGEF) contain an RH domain and are specific GEFs for t

184 construct associated with the endogenous PDZ-RhoGEF.

185 cific guanine nucleotide exchange factor PDZ-RhoGEF (Arhgef11) in white adipose tissue biology.

186 -Rho guanine nucleotide exchange factor (PDZ-RhoGEF) that was associated with and inhibited by microt

187 tin cytoskeleton as a novel function for PDZ-RhoGEF, thus implicating actin interaction in organizing

188 anine nucleotide exchange factor (GEF)), PDZ-RhoGEF, and p115RhoGEF augmented interaction between act

189 nine nucleotide exchange factors (GEFs), PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), use their

190 e also show that two of these RhoA GEFs, PDZ-RhoGEF and leukemia-associated RhoGEF (LARG), link bombe

191 define a novel actin-binding sequence in PDZ-RhoGEF with a critical amino acid motif of IIxxFE.

192 nce of a novel 25-amino acid sequence in PDZ-RhoGEF, located at amino acids 561-585, that is necessar

193 change factors (RhoGEFs), which includes PDZ-RhoGEF (PRG) and leukemia-associated RhoGEF (LARG).

194 ange factors (RGL-RhoGEFs) that includes PDZ-RhoGEF (PRG), p115RhoGEF, and LARG, thereby regulating c

195 12/13 GPCRs to Rho activation, including PDZ-RhoGEF (PRG), leukemia-associated Rho GEF (LARG), p115-R

196 Last, PDZ-RhoGEF mutants that fail to interact with the actin cyto

197 On a whole organism level, PDZ-RhoGEF deletion resulted in an acute increase in energy

198 Mechanistically, PDZ-RhoGEF enhanced insulin/IGF-1 signaling in adipose tissu

199 F and leukemia-associated RhoGEF but not PDZ-RhoGEF.

200 Deletion of the C-terminal tail of PDZ-RhoGEF had no significant effect on the GEF catalytic ac

201 erization of the actin-binding region of PDZ-RhoGEF revealed a dimerization-dependent actin bundling

202 el mechanism controlling the activity of PDZ-RhoGEF, LARG, and p115RhoGEF, which involves homo- and h

203 the peri-plasma membrane localization of PDZ-RhoGEF.

204 exinB2 in complex with the PDZ domain of PDZ-RhoGEF.

205 licating actin interaction in organizing PDZ-RhoGEF signaling.

206 change factors for the small GTPase Rho, PDZ-RhoGEF and LARG, and are mediated by the activation of R

207 ne nucleotide exchange factors (RhoGEFs) PDZ-RhoGEF and LARG that stimulate the GDP-GTP exchange rate

208 Unique among the RGS-RhoGEFs, PDZ-RhoGEF contains a short sequence that localizes the prot

209 Our results demonstrate that PDZ-RhoGEF acts as a key determinant of mammalian metabolism

210 Indeed, we observed that PDZ-RhoGEF and LARG can form homo- and hetero-oligomers, whe

211 cosedimentation assays demonstrate that PDZ-RhoGEF binds to actin.

212 as a dimer, raising the possibility that PDZ-RhoGEF could influence actin structure in a manner indep

213 This report demonstrates that PDZ-RhoGEF, a member of a subfamily of RhoGEFs that contain

214 L that mediates its interaction with the PDZ-RhoGEF protein.

215 F antiserum, we found that a transfected PDZ-RhoGEF construct associated with the endogenous PDZ-RhoG

216 endent signaling compared with wild-type PDZ-RhoGEF.

217 Unconventionally, PDZ-RhoGEF (PRG), a member of the RGS-RhoGEFs, binds tightly

218 While PDZ-RhoGEF was dispensable for a number of RhoA signaling-me

219 Taken together, results with PDZ-RhoGEF and frabin identify a novel actin-binding sequenc

220 rminus of the RhoGEF frabin, and as with PDZ-RhoGEF, mutagenesis and actin interaction experiments de

221 t the substrate utilization of a promiscuous RhoGEF family member.

222 ediated inhibition of RhoA and also recruits RhoGEFs to directly stimulate RhoA activity.

223 each now known to directly bind and regulate RhoGEFs.

224 F) family; however, mechanisms that regulate RhoGEFs are not well understood.

225 n contrast, p63RhoGEF, a Galpha(q)-regulated RhoGEF, appears to be constitutively localized to the PM

226 PCRs and effectors such as G alpha-regulated RhoGEFs, but also novel conformational changes that are

227 , as opposed to other known Galpha-regulated RhoGEFs, which are instead sequestered in the cytoplasm,

228 e known G protein-coupled receptor-regulated RhoGEFs are found in the cytoplasm of unstimulated cells

229 onal interaction between G alpha(13) and RGL-RhoGEFs based on the structure of RGL domains and their

230 Rho guanine nucleotide exchange factors (RGL-RhoGEFs) that includes PDZ-RhoGEF (PRG), p115RhoGEF, and

231 association results in the activation of RGL-RhoGEFs are still poorly understood.

232 2), which acts via the single C. elegans RGS RhoGEF (RHGF-1).

233 e GEF activity of p115-RhoGEF (p115), an RGS-RhoGEF, can be stimulated by Galpha(13), the exact mecha

234 ssociated RhoGEF (LARG), a RhoA-specific RGS-RhoGEF, is required for abscission, the final stage of c

235 into the mechanism of regulation of the RGS-RhoGEF and broadens our understanding of G protein signa

236 tor of G protein signaling (RGS) domain (RGS-RhoGEFs).

237 ct of this mutation in its regulation of RGS-RhoGEFs p115 or LARG.

238 Direct regulation of the activity of RGS-RhoGEFs p115 or leukemia-associated RhoGEF (LARG) by Gal

239 RGS-containing RhoGEFs (RGS-RhoGEFs) represent a direct link between the G(12) class

240 gnaling (RGS) domain-containing RhoGEFs (RGS-RhoGEFs) that link activated heterotrimeric G protein al

241 nally, PDZ-RhoGEF (PRG), a member of the RGS-RhoGEFs, binds tightly to both nucleotide-free and activ

242 Unique among the RGS-RhoGEFs, PDZ-RhoGEF contains a short sequence that local

243 lpha13 is important for interaction with RGS-RhoGEFs and is critically involved in the regulation of

244 RH-RhoGEFs are a family of guanine nucleotide exchange fact

245 leotide exchange factor (GEF) activity of RH-RhoGEFs, leading to activation of RhoA.

246 Galpha(13) stimulates the GEF activity of RH-RhoGEFs, such as p115RhoGEF, has not yet been fully eluc

247 em to rapidly control the localization of RH-RhoGEFs.

248 Lbc family of RhoGEFs which includes the RH-RhoGEFs.

249 Because all three RH-RhoGEFs can localize to the plasma membrane upon express

250 nge factors for the monomeric G protein Rho (RhoGEFs) are well characterized as effectors of this G p

251 s-specific role is independent of ARHGEF17's RhoGEF activity in interphase.

252 Based on the homology of our protein's RhoGEF domain to the RhoGEF domains of Trio, Duo and Due

253 of F-actin assembly, we uncovered a separate RhoGEF(Pbl)-dependent pathway that, at the normal time o

254 can facilitate increased activity of soluble RhoGEFs on vesicle-delimited substrate (RhoA-GDP).

255 essed UNC-73 isoforms contain a Rac-specific RhoGEF-1 domain, a Rho-specific RhoGEF-2 domain, or both

256 Rac-specific RhoGEF-1 domain, a Rho-specific RhoGEF-2 domain, or both domains.

257 provide evidence that developmentally staged RhoGEFs control assembly of two alternative forms of cle

258 WH2 domain, two SH3 domains and a C-terminal RhoGEF (DH)-PH domain.

259 ese observations support the hypothesis that RhoGEFs, particularly LARG, participate in linking GPCR

260 The RhoGEF Ect2 controls cell division and exerts oncogenic

261 The RhoGEF mutant of p210 Bcr-Abl does not affect the tyrosi

262 rmal levels of tyrosine kinase activity, the RhoGEF mutant of p210 Bcr-Abl is impaired in transformin

263 vage furrow during cytokinesis, p190 and the RhoGEF Ect2 play opposing roles in cytokinesis, and sust

264 he RasGAP Syngap1, the ArfGAP Agap2, and the RhoGEF Kalirin, which includes a total of 280 interactio

265 In reconstitution assays, the RhoGEF activity of nonphosphorylated LARG was stimulated

266 guanine exchange factors (RhoGEFs), but the RhoGEF(s) required for LTP also remain unknown.

267 During cytokinesis, RhoA is activated by the RhoGEF ECT-2.

268 Galpha(12)/Galpha(13) or their effector, the RhoGEF protein LARG, RhoA-dependent SRF-regulation was b

269 n of Galpha13 impaired its regulation of the RhoGEF activity of p115 or LARG.

270 oA observed by overexpression of five of the RhoGEF DH-PH domains.

271 actin-binding motif in the N-terminus of the RhoGEF frabin, and as with PDZ-RhoGEF, mutagenesis and a

272 re, we delineate a pathway downstream of the RhoGEF Pbl/Ect2 that directs this process in a model epi

273 PTTG1-dependent expression of the RhoGEF proto-oncogene ECT2 was observed in a number of c

274 by Tec, Galpha12 effectively stimulated the RhoGEF activity of LARG.

275 Activated Galpha13 stimulated the RhoGEF activity of p115 through interaction with the N-t

276 l mechanism by which Galpha13 stimulates the RhoGEF activity of these proteins has not yet been well

277 al, and imaging techniques, we show that the RhoGEF Kalirin and its paralog Trio play critical and re

278 Silencing studies show that the RhoGEF Trio is crucial for keeping active Rac1 at the do

279 210 Bcr-Abl to interact with XPB through the RhoGEF domain.

280 ain-of-function activity attributable to the RhoGEF domain of p210 Bcr-Abl that is required to suppor

281 mology of our protein's RhoGEF domain to the RhoGEF domains of Trio, Duo and Duet and its homology wi

282 ne kinase activity, and mutations within the RhoGEF domain that are predicted to eliminate RhoGEF act

283 We found that, among the RhoGEFs tested, MCP1 induced tyrosine phosphorylation of

284 Here, we sought to identify the RhoGEFs involved in monocyte chemotactic protein 1 (MCP1

285 s not modulate the intrinsic activity of the RhoGEFs, activated RhoA associated with phospholipid ves

286 ecently been determined for several of these RhoGEFs and their G protein complexes, providing fresh i

287 ted Galpha13, cellular localization of these RhoGEFs has been proposed as a mechanism for controlling

288 can bind and regulate the activity of these RhoGEFs, thus providing a direct link from these heterot

289 nge factor (GEF) activity toward RhoA, these RhoGEFs also possess RGS homology (RH) domains that inte

290 has been shown in mammalian cells that these RhoGEFs interact with activated forms of G alpha 12 or G

291 This RhoGEF has an essential role in cytokinesis, but also pl

292 ave identified new, essential roles for this RhoGEF in ciliated epithelia during vertebrate developme

293 Three RhoGEF isoforms are produced by the gene ARHGEF25; p63Rh

294 e G12 family regulate the Rho GTPase through RhoGEFs that contain an amino-terminal regulator of G pr

295 rotein 90 (Hsp90) while retaining binding to RhoGEFs.

296 ons in both EGL-8 (PLCbeta) and UNC-73 (Trio RhoGEF) have strong synthetic phenotypes that phenocopy

297 Activated Galpha(q) and Trio RhoGEF appear to be part of a signaling complex, because

298 ic G protein Galphaq, and its effector, Trio RhoGEF.

299 ed C. elegans Galpha(q) synergizes with Trio RhoGEF to activate RhoA.

300 with F-actin and myosin II, which are under RhoGEF(Pbl)-dependent control themselves.