ライフサイエンスコーパス: RasGAP

1 RasGAP (p120RasGAP), the founding member of the GTPase-a

2 RasGAP (Ras GTPase-activating protein) is a negative reg

3 RasGAP and Shc were also found to associate with GRB2 in

4 RasGAP residues 890-902 (block 3A) were observed to be h

5 RasGAP used its N-terminal Src homology 2 domain to bind

6 RasGAP, that responds to activation of PDGFR-beta but no

7 RasGAP, which associates with PDGFRbeta but not PDGFRalp

8 Neurofibromin, the product of NF1, acts as a RasGAP and suppresses growth; inactivating mutations in

9 melanoma exomes identified RASA2, encoding a RasGAP, as a tumor-suppressor gene mutated in 5% of mela

10 Third, recruiting a RasGAP, RASAL3, to cell fronts extinguished protrusions

11 ated and co-immunoprecipitates with Bcr-Abl, RasGAP, and CrkL, a Src homology 2 (SH2) and SH3 domain-

12 omain protein RGBARG (RCC1, RhoGEF, BAR, and RasGAP-containing protein).

13 differences between RasGAP-EphB4 binding and RasGAP-p190RhoGAP binding.

14 ors of the EGFR pathway, including c-Cbl and RasGAP, and more than that of MAPK phosphatase.

15 The opposing actions of CSW and RasGAP modulate the strength of the Torso signal, contri

16 tigated the interaction between p62(dok) and RasGAP and the consequences of p62(dok) tyrosine phospho

17 n mast cells via recruitment of p62(dok) and RasGAP.

18 Furthermore, PLC gamma and RasGAP negatively modulate PDGF-dependent PI3K activatio

19 binds directly to the SH2 domain of Nck and RasGAP and indirectly to NIK bound to the SH3 domain of

20 ast, receptors that associated with PI3K and RasGAP or PI3K and PLC gamma displayed a greatly reduced

21 ity of RasGAP, the interactions with Ras and RasGAP may fine-tune Ras signaling.

22 light the dynamic balance between RasGEF and RasGAP in these T-ALLs and put forth a new model in whic

23 dulate Ras activity using various RasGEF and RasGAP proteins and assess their effects on migration dy

24 activation of the PLCgamma, PI3K, SHP2, and RasGAP pathways still retain partial ability to induce 6

25 1 (TIA-1), TIA1-related protein (TIAR), and RasGAP-SH3 domain binding protein 1 (G3BP1) are required

26 utionarily conserved surface centered around RasGAP residue R707, point mutation of which impairs the

27 g reveals conformational differences between RasGAP-EphB4 binding and RasGAP-p190RhoGAP binding.

28 ropose that the physical interaction between RasGAP and FLN-C facilitates an interaction between G3BP

29 This region binds RasGAP and contains serine 149 whose dephosphorylation i

30 These results highlight the role played by RasGAP in FGFR signaling and how graded stress intensiti

31 ited (i) the cleavage of RasGTP to RasGDP by RasGAP; (ii) the binding to RasGTP of Raf-1, phosphatidy

32 are activated by RasGEFs and inactivated by RasGAPs, which stimulate the hydrolysis of RasGTP to ina

33 romin that is present in all known canonical RasGAPs.

34 of cells to form stress granules by cleaving RasGAP-SH3-binding protein (G3BP).

35 Under mild stress conditions, RasGAP is cleaved by caspase-3 at position 455.

36 Consequently, RasGAP undergoes a conformational change that results in

37 forth a new model in which IL-2/7/9 decrease RasGAP activity.

38 stress intensities, by generating different RasGAP fragments, can positively or negatively impact th

39 misregulation by using cells with disrupted RasGAP activity.

40 ntly to a complex between NIK/Nck, p62(dok), RasGAP, and an unidentified 145-kDa tyrosine-phosphoryla

41 Pase-activating proteins (RasGAPs) with dual RasGAP/RapGAP specificity, is epigenetically silenced in

42 In contrast to mice lacking either RasGAP alone in T cells, double-deficient mice developed

43 3K as well as one additional protein, either RasGAP, SHP-2, or PLC gamma.

44 pin RNA interference to knock out endogenous RasGAP expression.

45 IqgC interacts with active RasG and exhibits RasGAP activity toward this GTPase.

46 demonstrate a 100-fold weakened affinity for RasGAP-EphB4 binding compared to RasGAP-p190RhoGAP or Ra

47 Rasal and Ras in the membrane essential for RasGAP activation, but direct and Ca-dependent interacti

48 development, supporting an effector role for RasGAP.

49 be provoked by the release of cdk7 mRNA from RasGAP SH3 domain-binding protein, G3BP, and its subsequ

50 y and call for repositioning of this genuine RasGAP outside of the IQGAP group.

51 und that huntingtin is associated with Grb2, RasGAP, and tyrosine-phosphorylated EGF receptor.

52 first time to our knowledge, the entire HRas-RasGAP protein complex in a QM/MM simulation context.

53 e involved in GTP hydrolysis within the HRas.RasGAP system is analyzed using a tailored approach base

54 buted to the Dictyostelium ortholog of human RasGAP NF1, in commonly used axenic laboratory strains,

55 entical to p62(dok-1), a recently identified RasGAP binding protein from CML cells, and analysis of t

56 s do not impact catalytic activity, implying RasGAP utilizes its SH2 domains to achieve diverse spati

57 oximal to their canonical GAP domain, and in RasGAP (p120GAP, p120RasGAP; RASA1) mutation of this dom

58 s 1099-1129 have no structural equivalent in RasGAP and are seen to form an extension at one end of t

59 overexpression of Dok-1 that was mutated in RasGAP-binding domain.

60 signaling or regulatory proteins, including RasGAP, AP-2, p53BP-2 (p53-binding protein-2), interleuk

61 at tyrosine-phosphorylated p62(dok) inhibits RasGAP activity.

62 ted in infected cells despite lacking intact RasGAP SH3-domain binding protein 1 (G3BP) and eukaryoti

63 and lipids, which simultaneously induces its RasGAP activity through a yet unknown mechanism.

64 activation of phosphatidylinositol 3-kinase, RasGAP, SHP-2, phospholipase C-gamma, and Src are not ne

65 Hence, full-length RasGAP favors Akt activity by shielding it from deactiva

66 Local RasGAP recruitment suppresses protrusions, generates new

67 eins but observed the stress granule markers RasGAP SH3-binding protein and phosphorylated eukaryotic

68 not at the cell surface to inhibit multiple RasGAPs, resulting in sustained Ras activation.

69 act with both Ras and p120RasGAP (also named RasGAP).

70 undary formation, as well as binding of Nck, RasGAP, and the chimaerins, respectively.

71 utant of KRAS in complex with neurofibromin (RasGAP domain) provide the structural basis for neurofib

72 se-activating protein (SynGAP) is a neuronal RasGAP (Ras GTPase-activating protein) that is selective

73 firming that exon 23a inclusion inhibits Nf1 RasGAP activity in vivo as it does in cultured cells.

74 stem cell-derived neurons indicated that Nf1 RasGAP activity is modulated by the highly regulated alt

75 for the Ras small G proteins, yet it has no RasGAP activity and binds to the Rho family small G prot

76 IQGAP1, a novel RasGAP-related protein that interacts with the cytoskele

77 d cells via recruitment and/or activation of RasGAP, and that preventing this negative feedback mecha

78 does not increase the catalytic activity of RasGAP, the interactions with Ras and RasGAP may fine-tu

79 tyrosine phosphorylation on the activity of RasGAP.

80 DF-1alpha/CXCL12 enhanced the association of RasGAP with Pyk2.

81 We found that binding of RasGAP to the wild-type betaPDGFR was decreased; the act

82 the phosphotyrosine required for binding of RasGAP.

83 the SHP2 active site, leading to blockade of RasGAP binding and optimal signaling by the two receptor

84 the rapid recruitment to the cytoskeleton of RasGAP (p120RasGAP), its associated protein of 190 kilod

85 is achieved through the dephosphorylation of RasGAP binding sites at the level of the plasma membrane

86 Here, we show that the C2 domain of RasGAP is required for full catalytic activity toward Ra

87 We find that the Drosophila homolog of RasGAP associates with pY918 and is a negative effector

88 nvestigated in Xenopus oocytes the impact of RasGAP and its fragments on FGF1-mediated signaling duri

89 st that SC1 works through dual inhibition of RasGAP and ERK1.

90 Knockdown of RasGAP or FLN-C, or severing their interaction, resulted

91 Knockdown of RasGAP resulted in a similar enhancement of CrkI transfo

92 In vivo, loss of RasGAP in Schwann cells, unlike the loss of merlin, fail

93 On the other hand, overexpression of RasGAP induced a Cdk7- and FLN-C-dependent growth.

94 Overexpression of RasGAP or a mutant lacking the GTPase-activating domain

95 To identify partners of RasGAP we used it as the bait in a yeast two-hybrid scre

96 on fibronectin diminished the recruitment of RasGAP to the betaPDGFR, we focused on SHP-2 since it de

97 most highly conserved amino acid residues of RasGAP were changed by mutation.

98 indicate a previously unappreciated role of RasGAP in antagonizing indirect activation of PDGFRbeta,

99 To determine the role of RasGAP in receptor-mediated activation of Akt, we used s

100 de between the active anticancer sequence of RasGAP and DLC1.

101 Previous structural studies of RasGAP have failed to clearly localize sites of Ras inte

102 e phosphorylation-dependent translocation of RasGAP to the plasma membrane, to its substrate (GTP-Ras

103 his study we provide a detailed viewpoint of RasGAP recruitment to various binding partners and asses

104 anoma driver and highlight the importance of RasGAPs in cancer.

105 hese studies highlight the expanding role of RasGAPs and reveal an alternative mechanism of activatin

106 binding partners and assess their impact on RasGAP activity.

107 on cell motility or polarity, we focused on RasGAPs, C2GAPB in Dictyostelium amoebae and RASAL3 in H

108 studies indicate that SH3 domains of Grb2 or RasGAP are required for their binding to huntingtin.

109 hB4 binding compared to RasGAP-p190RhoGAP or RasGAP-Dok1 binding, possibly driven by single versus du

110 p120 RasGAP (GTPase-activating protein), which contains an SH

111 The caspase-3/p120 RasGAP module is a stress sensor switch.

112 rc homology 3 domain of p200 RhoGAP and p120 RasGAP, respectively.

113 RASA1 (also known as p120 RasGAP) is a Ras GTPase-activating protein that function

114 ations of the RASA1 gene, which encodes p120 RasGAP (RASA1), a negative regulator of the Ras small GT

115 is very similar to the GAP domains from p120 RasGAP, neurofibromin, and SynGAP.

116 nd the SH2 domains of the Ras inhibitor p120 RasGAP.

117 We found the Ras suppressor p120 RasGAP (RASA1) harbored a genome-wide significant burden

118 se model to investigate the role of the p120 RasGAP (RASA1) in T cells.

119 00 RhoGAP that disrupt interaction with p120 RasGAP abolish its Ras activation and cell transforming

120 kDa protein that stably associates with p120 RasGAP and regulates actin dynamics through members of t

121 p200 RhoGAP co-localizes with p120 RasGAP in cells and forms a complex with p120 RasGAP, an

122 hesize that the association of FAK with p120 RasGAP may facilitate Ras activity.

123 = 1.22 x 10(-5)), which cooperates with p120 RasGAP to regulate vascular development.

124 asGAP in cells and forms a complex with p120 RasGAP, and this interaction is mediated by the C-termin

125 PXXP motifs, and the ability to bind to p120(RasGAP).

126 ctivation reaction catalyzed by SOS and p120-RasGAP on supported lipid membrane microarrays.

127 , had an increased abundance of cleaved p120-RasGAP compared to that in cells from healthy controls.

128 e found that in the presence of cleaved p120-RasGAP, CD200R lost its capacity to inhibit phosphorylat

129 esulted in increased amounts of cleaved p120-RasGAP.

130 and the GTPase activating protein (GAP) p120-RasGAP, which can be cleaved during mild cellular stress

131 RAFTK is associated with p190 RhoGAP (p190), RasGAP and ErbB-2, and plays an essential role in mediat

132 ceptor-associated proteins such as PLCgamma, RasGAP, Shc, and SHP-2 and for maximal activation of Erk

133 exinA2 co-expressed by GCs, and the PlexinA2-RasGAP activity is necessary to suppress spinogenesis.

134 protein is a Ras GTPase-activating protein (RasGAP) [2].

135 NF1 encodes a Ras GTPase-activating protein (RasGAP) and its loss drives cancer by activating Ras.

136 tudies of the Ras GTPase activating protein (RasGAP) and the elongation factor-Tu (EF-Tu) with a 1 W

137 hosphorylated Ras GTPase-activating protein (RasGAP) and upregulated RasGAP activity.

138 ecruitment of Ras GTPase-activating protein (RasGAP) by Dok-1, and inhibited activation of the mitoge

139 to a putative Ras GTPase-activating protein (RasGAP) from the fission yeast Schizosaccharomyces pombe

140 t loss of the Ras GTPase-activating protein (RasGAP) gene DAB2IP induces metastatic prostate cancer i

141 reported that Ras GTPase-activating protein (RasGAP) is involved in a pathway that regulates total ce

142 d on RASA2, a RAS GTPase-activating protein (RasGAP) that we identify as a signalling checkpoint in h

143 ecruitment of Ras GTPase-activating protein (RasGAP) to the plasma membrane through dephosphorylation

144 s not bind to Ras GTPase-activating protein (RasGAP) upon phosphorylation.

145 e, encoding a Ras GTPase activating protein (RasGAP), and elucidate the mechanism producing crisis ep

146 n (Nck), p120-Ras GTPase-activating protein (RasGAP), and the alpha- and beta-Chimaerin Rac GAPs.

147 ates with the Ras GTPase-activating protein (RasGAP), but only when p62(dok) is tyrosine phosphorylat

148 ts, including Ras GTPase-activating protein (RasGAP), cyclin-dependent kinase 9 (Cdk9), fibronectin,

149 gment of p120 Ras GTPase-activating protein (RasGAP), sensitizes tumor cells to apoptosis induced by

150 de is the Nf1 Ras GTPase activating protein (RasGAP), which attenuates Ras/ERK signaling by convertin

151 A 62-kDa Ras GTPase-activating protein (RasGAP)-associated protein is tyrosine-phosphorylated un

152 unctions as a Ras-GTPase activating protein (RasGAP).

153 catalyzed by Ras GTPase-activating protein (RasGAP).

154 omains of the Ras GTPase-activating protein (RasGAP).

155 ween Ras and its GTPase-activating proteins (RasGAP and NF1) has provided important insights into the

156 nknown which Ras GTPase-activating proteins (RasGAPs) inactivate Ras in T cells.

157 Ras GTPase-activating proteins (RasGAPs) inhibit signal transduction initiated through t

158 ms involving Ras GTPase activating proteins (RasGAPs) responsible for terminating Ras activity on ear

159 subfamily of Ras GTPase-activating proteins (RasGAPs) with dual RasGAP/RapGAP specificity, is epigene

160 amma), the GTPase-activating protein of Ras (RasGAP), and the tyrosine phosphatase SHP-2.

161 e Cdc42-Cdc42GAP complex, as well as the Ras-RasGAP complex, it has been proposed that an arginine re

162 raction similar to that displayed in the Ras-RasGAP complex, we created an energy-minimized model of

163 action of Rasal with membranes induces Rasal RasGAP activity by spatial and conformational regulation

164 t is unclear how SHP2 selectively recognizes RasGAP-binding sites on EGFR and HER2.

165 binds to SHIP and both Dok1 and Dok2 recruit RasGAP, which mediates the inhibition of the Ras/MAPK pa

166 rom associating with the negative regulator, RasGAP (the GTPase-activating protein of Ras).

167 systems, optically recruiting the respective RasGAP to the cell front extinguished pre-existing protr

168 However, when these respective RasGAPs were recruited uniformly to the membrane, cells

169 dentity with almost the entire S. pombe sar1 RasGAP homolog.

170 that SynGAP, an excitatory synapse-specific RasGAP, regulates AMPAR trafficking, silent synapse numb

171 GTPase activating protein tumor suppressor (RasGAP), DAB2 interacting protein (DAB2IP), was discover

172 TAT-RasGAP(317-326) is a cell-penetrating peptide-based cons

173 TAT-RasGAP(317-326) is an AMP with broad range antibacterial

174 e elucidated the mode of action allowing TAT-RasGAP(317-326) to kill cells.

175 responsible for the interaction between TAT-RasGAP(317-326) and BamA.

176 activity was only partially affected by TAT-RasGAP(317-326), indicating that BamA may function as a

177 sults indicate that binding and entry of TAT-RasGAP(317-326) may involve different mechanisms compare

178 This work shows that TAT-RasGAP(317-326) kills cells via a form of necrosis that

179 esenting a predictive fingerprint of the TAT-RasGAP(317-326) - BamA interaction strength.

180 richia coli with extensive resistance to TAT-RasGAP(317-326) but not to other AMPs that we obtained a

181 in cells renders them more resistant to TAT-RasGAP(317-326), while reducing the ability of cells to

182 loop decreased sensitivity of E. coli to TAT-RasGAP(317-326).

183 The W317A TAT-RasGAP(317-326) point mutant, known to have impaired kil

184 It has been proposed that RasGAP may also function as an effector of Ras activity.

185 In this paper, we report that RasGAP (GTPase-activating protein of Ras) prevented indi

186 This suggests that RasGAP and PKA may mediate common pathways that regulate

187 PDGFR, which in turn decreases the time that RasGAP interacts with the receptor.

188 The RasGAP-mediated polarization depended critically on myos

189 g (CRIB) motif-containing molecules, and the RasGAP domain containing IQGAP1 and IQGAP2.

190 e p21-binding domains of PAK1, PAK2, and the RasGAP-related domain of IQGAP1, which all cause signifi

191 d p21(cdc42/rac)-activated kinase 1, and the RasGAP-related domain of IQGAP1, which all inhibit the i

192 nase PAK, the tyrosine kinase ACK-2, and the RasGAP-related protein IQGAP.

193 A cDNA for p62(dok), reported to be the RasGAP-associated 62-kDa protein, was recently cloned fr

194 Using chimeric FcgammaRIIB containing the RasGAP-binding domain of p62dok, we demonstrate that p62

195 This gene encodes the RasGAP Neurofibromin (NF1).

196 GAP (trans-glutamine); this differs from the RasGAP mechanism, where the cis-glutamine is also import

197 ion, it appears that the role of p190 in the RasGAP signaling complex is to promote additional protei

198 g GAP/GEF proteins at the PSD, including the RasGAP Syngap1, the ArfGAP Agap2, and the RhoGEF Kalirin

199 Analyses of the RasGAP C2-GAP crystal structure, AlphaFold models, and s

200 However, which members of the RasGAP family act as negative regulators of T cell respo

201 proteins in vivo by genetic deletion of the RasGAP protein Nf1 and examined mice doubly deficient in

202 haracterized the Drosophila homologue of the RasGAP-binding protein G3BP encoded by rasputin (rin).

203 to increased tyrosine phosphorylation of the RasGAP-binding protein p62dok, with a concomitant increa

204 the expression of a noncleavable form of the RasGAP-SH3 domain binding protein in PV-infected cells e

205 d the interaction between RhoA and p190, the RasGAP binding phosphoprotein which has been implicated

206 erved ubiquitination pathways regulating the RasGAP proteins Ira2 (in yeast) and neurofibromin (in hu

207 stingly, a mutant receptor that restores the RasGAP-binding site promotes induction of an independent

208 We reveal the RasGAP SH2 domains generate distinct binding interaction

209 Here, we report that the RasGAP gene, RASAL2, functions as a tumor and metastasis

210 in vivo mouse experiments, we found that the RasGAP protein Rasal1 is a central mediator of plexin si

211 s is part of the cell's compass and that the RasGAP-mediated regulation of Ras activity affects direc

212 In contrast to the RasGAP mechanism, an accumulation of a state in which ph

213 ides in p190 that bind simultaneously to the RasGAP SH2 domains upon p190 phosphorylation.

214 RED1 binds directly to both c-KIT and to the RasGAP, neurofibromin, whose function is completely depe

215 n ring, and patches become enlarged when the RasGAP NF1 is mutated, showing that Ras plays an instruc

216 udy, we investigated potential roles for the RasGAPs RASA1 and neurofibromin 1 (NF1) in T cells throu

217 Moreover, none of the RasGAPs characterized so far have been implicated in the

218 This RasGAP-derived peptide, by targeting the deleted in live

219 erefore, modulation of Ras signaling through RasGAP likely contributes to, but is not sufficient to a

220 We evaluated intracellular signaling through RasGAP-associated protein p62Dok-1 (downstream of tyrosi

221 of Dok-related proteins exists that bind to RasGAP and may mediate the effects of p210(bcr-abl) in C

222 ith a concomitant increase in its binding to RasGAP.

223 ffinity for RasGAP-EphB4 binding compared to RasGAP-p190RhoGAP or RasGAP-Dok1 binding, possibly drive

224 -activating protein (RasGAP) and upregulated RasGAP activity.

225 We used RasGAP SH3-binding protein (G3BP) overexpression to indu

226 osine residues that are involved in in vitro RasGAP binding and have found that tyrosine-phosphorylat

227 dependently of its ability to associate with RasGAP and Nck.

228 tor-phosphorylated IRS5/DOK4 associates with RasGAP, Crk, Src, and Fyn, but not phosphatidylinositol

229 , preventing PDGFRbeta from associating with RasGAP allowed it to signal enduringly and drive pathoge

230 yrosine phosphorylation and association with RasGAP are observed, suggesting that SHIP may mediate Fc

231 yrosine phosphorylation and association with RasGAP, adaptor protein p46Nck, and Crk-L in Jurkat T ce

232 promote additional protein interactions with RasGAP via its SH3 domain.

233 pendent endoribonuclease that interacts with RasGAP, is recruited to SGs in cells exposed to arsenite