ライフサイエンスコーパス: Ras protein

1 antigenic sites, or the presence of a mutant RAS protein.

2 ed to glutathione beads to isolate activated ras protein.

3 uman intrabodies which bind to the oncogenic RAS protein.

4 tively with the stress elicited by oncogenic Ras protein.

5 vularia lunata, which is homologous with the Ras protein.

6 inhibit the post-translational processing of RAS proteins.

7 luster formation by crosslinking constituent Ras proteins.

8 d for optimal plasma membrane association of RAS proteins.

9 s recently been proposed for the H-Ras and M-Ras proteins.

10 ure regarding interactions between IQGAP and Ras proteins.

11 tochondria in the subcellular trafficking of Ras proteins.

12 mbrane attachment and biological activity of Ras proteins.

13 tes expressing the oncogenic forms of Raf or Ras proteins.

14 ion of Ras-GAP and thereby the activation of Ras proteins.

15 lled neurofibromin that negatively regulates Ras proteins.

16 could lead to increased potency of oncogenic Ras proteins.

17 stem for the plasma membrane localization of Ras proteins.

18 lmitoylation and subcellular localization of Ras proteins.

19 involved in the plasma membrane targeting of Ras proteins.

20 quate subcellular distribution of S-acylated Ras proteins.

21 gies and well-defined binding pockets on the Ras proteins.

22 llular distribution and activity of K- and H-Ras proteins.

23 molecule inhibitors that directly target the Ras proteins.

24 ivators increasing GTPase activity of mutant RAS proteins.

25 utations in RAS genes or otherwise activated RAS proteins.

26 n cells partially dependent on expression of RAS proteins.

27 been considered representative of all three Ras proteins.

28 be feasible to develop direct inhibitors of RAS proteins.

29 potential binding partners for farnesylated Ras proteins.

30 egies for inhibiting and depleting oncogenic RAS proteins.

31 roaches under investigation to target mutant RAS proteins.

32 We identified dexamethasone-induced Ras protein 1 (Dexras1) as a negative regulator of prote

33 is similar to those of GDP or GTP analogs in ras proteins, a prototype GTPase.

34 Ras proteins accelerate GTP hydrolysis by a factor of 10

35 Ras proteins activate Raf and PI-3 kinases, as well as e

36 Given that oncogenic Ras proteins activate the transcription factor NF-kappaB

37 re unsolved, and it is unknown precisely how Ras proteins activate their downstream targets.

38 Ras proteins activate three primary classes of effectors

39 The Ras protein acyltransferase (PAT) consists of a complex

40 ccharomyces cerevisiae is palmitoylated by a Ras protein acyltransferase (Ras PAT) encoded by the ERF

41 One of the loci is zDHHC9, a gene encoding a Ras protein acyltransferase.

42 tion leads to a constitutively active mutant Ras protein and activation of downstream signaling event

43 Total H-ras protein and cyclin D1 were found to increase during

44 s of guanosine triphosphate-bound (active) H-ras protein and cyclin E were increased during the putat

45 tein kinase C that is activated by oncogenic Ras protein and is required for K-Ras-induced transforma

46 f YAP were associated with activation of the RAS protein and its downstream AKT and ERK.

47 Mx1-Cre, LSL-Nras(G12D) mice show much lower Ras protein and Ras-GTP levels.

48 rase reporter and strikingly increased the K-ras protein and the downstream effectors ERK1/2 and B-Ra

49 F exhibiting high binding affinities for all RAS proteins and BRAF exhibiting increased binding affin

50 Ras proteins and cAMP-dependent protein kinase (protein

51 that is instead driven by palmitoylated H/N-RAS proteins and CRAF.

52 ent advances in therapies that target mutant RAS proteins and discuss the future challenges of these

53 s in the extreme C terminus of the different Ras proteins and farnesylation of the CaaX box cysteine

54 These activations were mediated through Ras proteins and GPR40, a receptor expressed on the surf

55 ence for a tumour suppressive role of kappaB-Ras proteins and highlight low kappaB-Ras levels and con

56 a functional relationship between endogenous RAS proteins and identify a dynamic physical interaction

57 Proliferation of cells lacking both Ras proteins and p53 can be prevented by reexpression of

58 04 also inhibits the activities of wild-type Ras proteins and Ras oncoproteins.

59 s terminating with a CAAX motif, such as the Ras proteins and the nuclear lamins, undergo post-transl

60 One such pathway, whose components include Ras proteins and the PAK kinase Ste20, allows the human

61 n interactions, including the interaction of RAS proteins and their effectors, may provide chemical p

62 p21(ras) (Ras) proteins and GTPase-activating proteins (GAPs) tigh

63 en in the context of mutation of the cognate Ras protein, and only relatively weak effects are detect

64 Despite extensive efforts to target mutated RAS proteins, anticancer agents capable of selectively k

65 The Ras proteins are aberrantly activated in a wide range of

66 riginates in differences in the way in which Ras proteins are activated by ligands of varying potency

67 f intracellular cAMP and the active forms of Ras proteins are also elevated in the ubp3Delta mutant.

68 kappaB-Ras proteins are also required for acinar regeneration a

69 ns that result in constitutive activation of RAS proteins are associated with approximately 30% of al

70 Ras proteins are binary switches that, by cycling throug

71 RAS proteins are binary switches, cycling between ON and

72 mice have provided evidence that H-Ras and K-Ras proteins are bioequivalent.

73 Oncogenic mutant Ras proteins are commonly expressed in human tumors, wit

74 Whereas both Ras proteins are constitutively activated, 32D cells exp

75 Ras proteins are critical nodes in cellular signaling th

76 RAS proteins are critical regulators of mitosis and are

77 RAS proteins are difficult to target pharmacologically;

78 Ras proteins are essential components of signal transduc

79 The Ras proteins are essential GTPases involved in the regul

80 ctural and biochemical properties, oncogenic Ras proteins are exceedingly difficult targets for ratio

81 Ras proteins are founding members of a large superfamily

82 The RAS proteins are GTP-dependent switches that regulate si

83 Ras proteins are highly conserved signaling molecules th

84 RAS proteins are important direct activators of p110alph

85 Mutant Ras proteins are important drivers of human cancers, yet

86 Dynamic clusters of lipid-anchored Ras proteins are important for high-fidelity signal tran

87 Ras proteins are important signalling hubs frequently dy

88 Ras proteins are major regulators of chemotaxis in Dicty

89 Ras proteins are members of a superfamily of related sma

90 Ras proteins are membrane bound signalling hubs that ope

91 Ras proteins are modified by farnesyltransferase (FTase)

92 B-Raf and N-Ras proteins are often activated in melanoma, yet their

93 Although RAS proteins are often said to be "undruggable," there i

94 Ras proteins are organized into membrane nanoclusters, w

95 Most Ras proteins are posttranslationally modified by a palmi

96 Understanding how Ras proteins are regulated is important for elucidating

97 RAS proteins are signal transduction gatekeepers that me

98 Ras proteins are small GTPases that act as signal transd

99 RAS proteins are small GTPases that play a central role

100 Ras proteins are small GTPases that regulate cellular gr

101 Ras proteins are small GTPases with well known functions

102 Ras proteins are synthesized as cytosolic precursors, bu

103 In general, Ras proteins are thought to promote cardiac hypertrophy,

104 hibiting conditions, indicating that RasC or RasD proteins are essential for GSK3-mediated PKBR1 inhi

105 ression of both wild-type Harvey and Kirsten Ras proteins as contributors to rat mammary carcinogenes

106 Ras proteins associate with cellular membranes as a cons

107 the G12D and G13D oncogenic mutants of the K-Ras protein bound to a negatively charged lipid bilayer.

108 ine that contains high levels of wild-type H-ras protein but no H-rasV(12) mutation), introduction of

109 cells, G protein-coupled receptors activate Ras proteins, but it is unclear how Ras-associated pathw

110 Plants do not have Ras proteins, but they contain Rho-like small G proteins

111 njugates), and ISG15, in turn, stabilizes Ki-Ras protein by inhibiting its targeted degradation via l

112 icancer agents developed to target oncogenic Ras proteins by inhibiting Ras farnesylation.

113 therapeutic dilemma, as direct targeting of Ras proteins by small molecules has proved difficult.

114 Ras proteins can bring about activation of MEK1 and p42

115 However, a current model suggests that Ras proteins can compartmentalize to regulate different

116 Activation of RAS proteins can lead to multiple outcomes by virtue of

117 In vitro studies also suggest that WT Ras proteins can suppress the tumorigenic properties of

118 In the case of the Ras proteins, carboxyl methylation is important for targ

119 factor 1 (Ras-GRF1), a neuronal activator of Ras proteins, causes a specific loss of HFS-LTP in the m

120 lucidate the regulatory mechanism of the key Ras protein Clg2p in C. lunata.

121 RAS protein coclustering is mainly mediated by membrane

122 ore stable complexes with Rap2 and classical Ras proteins compared with Rap1.

123 RAS proteins concentrate in the plasma membrane via lipi

124 RAS proteins conduct signaling from surface receptors to

125 Using chimeric Ras proteins containing all combinations of Ras backgrou

126 Experiments have shown that homologous Ras proteins containing different lipid modification, wh

127 K-Ras proteins containing this tandem duplication or a sim

128 Active Ras proteins contribute to breast carcinogenesis and pro

129 Structural dynamics of Ras proteins contributes to their activity in signal tra

130 us to the dual-signal targeting mechanism of Ras proteins, cooperate to target heterotrimeric G prote

131 Moreover, IDabs selected for binding to the RAS protein could inhibit RAS-dependent oncogenic transf

132 Similarly, we found that mutant Ras proteins could be detected and quantified in clinica

133 Ras proteins cycle between GDP-bound and GTP-bound state

134 p21Ras (Ras) proteins cycle between active GTP-bound and inactiv

135 Pan-RAS protein degradation, however, affects proliferation

136 Mutant K-Ras proteins demonstrate a range of gain-of-function eff

137 RAS proteins directly activate PI3-kinases.

138 Phosphorylation of R-Ras proteins does not affect their subcellular localizat

139 Oncogenic activation of Ras proteins due to missense mutations is frequently det

140 direct protein-protein interactions, making RAS protein dynamics a critical determinant of RAS funct

141 HDX provides a means of evaluating Ras protein dynamics, which may be useful for understand

142 distinct lipid compositions, indicating that Ras proteins engage in isoform-selective lipid sorting a

143 tial to inactivate both wild-type and mutant Ras proteins expressed in malignancies.

144 12D) expression results in markedly elevated Ras protein expression and Ras-GTP levels in Mac1(+) cel

145 MIC-dependent tumor growth through promoting RAS protein expression and that cancer therapies targeti

146 These results show that the level of K-ras protein expression is a major determinant of prolife

147 own of HAGE led to a significant decrease in RAS protein expression with a concomitant decrease in ac

148 KRAS, a key member of the RAS protein family, is an attractive cancer target, as f

149 n was blocked by the structurally dissimilar Ras protein farnesyl transferase inhibitors manumycin-A

150 e molecular mechanism by which full-length H-ras proteins form nanoclusters in a model membrane.

151 t experiments have shown that membrane-bound Ras proteins form transient, nanoscale signaling platfor

152 analyze the nature of the pool of endogenous Ras proteins found in the cytosol.

153 Although vesicular transport of the H-Ras protein from the Golgi to the plasma membrane is wel

154 egion, modulates the effector selectivity of RAS proteins from H-RAS to E-RAS features.

155 l known, but the precise mechanisms by which RAS proteins function are less clear.

156 Ras proteins function as signaling hubs that are activat

157 tical for beta(2)-integrin adhesion and that Ras-protein functions as the common regulator for cytoki

158 Unlike Ras proteins, Gbetagamma contains a single targeting sig

159 Here, we found that Ras proteins (H-Ras and R-Ras) enhance SF-mediated activ

160 lved in the IGF-1 signaling, because another Ras protein, H-ras localized to the plasma membrane inde

161 Mammalian cells encode three closely related Ras proteins, H-Ras, N-Ras, and K-Ras.

162 Posttranslational processing of Ras proteins has attracted considerable interest as a po

163 region (residues 166-189), of H-, N-, and K-Ras proteins has sequence determinants necessary for ful

164 Ras proteins have a key role in the regulation of severa

165 ular and nonvesicular transport pathways for Ras proteins have been proposed, but the pathway is not

166 Unlike Ras, few activating mutations of R-Ras proteins have been reported in human cancer, and ver

167 Oncogenic Ras proteins have been shown to stimulate macropinocytos

168 The Ras proteins have been termed "undruggable," based on fa

169 lso highlight our previous observations that Ras proteins have functions in the absence of acute mito

170 However, Ras proteins have proven difficult to target directly.

171 Mutations of the Ras proteins HRAS, KRAS4A, KRAS4B, and NRAS are associat

172 om the growing appreciation that neither all RAS proteins (HRAS, NRAS, and KRAS4A/KRAS4B) nor all onc

173 Recently, the structure of the full-length H-ras protein in a DMPC bilayer has been computationally c

174 Here, the structure of the full-length H-Ras protein in complex with a 1,2-dimyristoylglycero-3-p

175 To analyze the functions of RAS protein in granulosa cells during ovarian follicular

176 tic domain, due to the prominent role of the Ras protein in signaling pathways that control cell prol

177 emonstrate that sp-Erf2/zDHHC9 palmitoylates Ras proteins in a highly selective manner in the trans-G

178 ht some important trends in the targeting of RAS proteins in cancer.

179 high affinity, thereby displacing prenylated Ras proteins in cells.

180 ing the differential properties of oncogenic Ras proteins in primary cells, for identifying candidate

181 terns evoked by ectopic production of Myc or Ras proteins in primary tissue culture cells properly pr

182 The role of the nonmutated, wild-type RAS proteins in the context of mutant RAS is increasingl

183 approach to this question, we activated all Ras proteins in vivo by genetic deletion of the RasGAP p

184 Post-translational modification of Ras proteins includes prenylcysteine-directed carboxyl m

185 bations that are propagated throughout the H-Ras protein including increased flexibility of the centr

186 Activated Ras proteins interact with a broad range of effector pro

187 The RAS proteins interact with a common set of activators an

188 two-hybrid assay revealed a p204-cytoplasmic Ras protein interaction.

189 We transduced dominant negative (dn) HIV TAT-Ras protein into mature human eosinophils to determine t

190 The lateral segregation of Ras proteins into transient plasma membrane nanoclusters

191 urate measurement of activity of wild-type K-ras protein is important due to its tumor suppressor act

192 ing between GDP- and GTP- bound forms of the Ras protein is partly regulated by the binding of Sos.

193 ung tumors than in normal lung tissue, while RAS protein is significantly higher in lung tumors, prov

194 ecognized that the functional versatility of Ras proteins is accomplished through their differential

195 Plasma membrane (PM) localization of Ras proteins is crucial for transmitting signals upon mi

196 the aberrant biochemical output of oncogenic Ras proteins is one of the great challenges in cancer th

197 In the case of Ras proteins, it has been suggested that the differentia

198 Thus, among four Ras proteins, K-Ras4A is unique in possessing a dual mem

199 ction signal transduction pathways including Ras, protein kinase A, target of rapamycin (TOR), phosph

200 Ins(4,5)P(2), resulting in the activation of Ras, protein kinase C and Ca(2+) flux.

201 s a filamentation program dependent upon the Ras-protein kinase A (PKA) pathway.

202 strong genetic interaction of DASH with the Ras/protein kinase A (PKA) pathway.

203 ce of interactions between the Nrd1-Nab3 and Ras/protein kinase A (PKA) pathways.

204 apping signaling networks--those centered on Ras/protein kinase A, AMP-activated kinase, and target o

205 d that several signaling pathways, including Ras/protein kinase A, AMP-activated kinase, the high-osm

206 localization, it selectively downregulated H-Ras protein levels at the post-translational level.

207 -, N-, or HRAS genes that encode an abnormal RAS protein locked in a constitutively activated state t

208 Therefore, differential ubiquitination of Ras proteins may control their location-specific signali

209 Ras proteins mediate PI3K activation through direct bind

210 Ras proteins mediate the proliferative effects of G-prot

211 E-RAS protein most remarkably revealed a different mode of

212 Ras proteins move between membrane compartments in part

213 r amphiphiles such as indomethacin influence Ras protein nanoclustering in intact plasma membrane.

214 expression of ERAS, a constitutively active RAS protein normally expressed only in embryonic stem ce

215 Like all RAS proteins, NRAS must undergo a series of post-transla

216 Mutations in RAS proteins occur widely in human cancer.

217 t signaling by oncogenic mutant rat sarcoma (Ras) proteins occurs in approximately 15% of all human t

218 mitochondrial defects and an accumulation of Ras proteins on mitochondrial membranes.

219 -PKB signaling mediates effects of activated Ras proteins on the cytoskeleton and cell migration.

220 Ras proteins on the inner leaflet of the plasma membrane

221 ctivated protein kinases (MAPK) by an active Ras protein or TGF-beta treatment significantly increase

222 ing geranylgeranylation for farnesylation on Ras proteins or vice versa on Rho proteins reversed the

223 Ras protein over-expression has been observed in human b

224 cal and functional studies of three mutant K-Ras proteins (P34R, D153V, and F156L) found in individua

225 y proliferation through dysregulation of the RAS protein pathway can lead to within-testis expansion

226 were an average of 1.3 million molecules of Ras protein per cell, and the ratio of mutant to normal

227 in the RAS genes or their regulators render RAS proteins persistently active.

228 Ras proteins play a central role in transducing signals

229 Ras proteins play a major role in human cancers but have

230 The RAS proteins play a role in cell differentiation, prolif

231 Ras proteins play vital roles in numerous biological pro

232 Post-translational lipid modification of Ras proteins plays an important role in their recruitmen

233 o quantify the number and fraction of mutant Ras protein present in cancer cell lines.

234 The activated Ras proteins produced by these mutations can, among othe

235 Only the RalGDS 37G-N-Ras protein protected the N-Ras knockout cells from apop

236 used compounds add to the growing catalog of RAS protein-protein inhibitors and show that building a

237 per cell, and the ratio of mutant to normal Ras proteins ranged from 0.49 to 5.6.

238 study Ras signaling because it has a single Ras protein, Ras1, that regulates two distinct pathways:

239 Like other Ras proteins, Ras1 is activated upon guanine triphosphat

240 e front of migrating cells downstream of the Ras protein RasC, controlling F-actin dynamics and cAMP

241 Ras proteins regulate a wide range of biological process

242 Ras proteins regulate cellular growth and differentiatio

243 Ras proteins regulate signal transduction processes that

244 Ras proteins regulate signaling pathways important for c

245 y activated in human cancers, but the mutant Ras proteins remain largely "undruggable" through the co

246 As Ras proteins require the membrane localization for the t

247 in antibody fragment (scFv) directed against Ras proteins results in radiosensitization.

248 Ras proteins share ~85% amino acid identity, are activat

249 Recombinant V14I and T58I K-Ras proteins show defective intrinsic GTP hydrolysis and

250 signaling cascade proteins (GO: 0007242) and Ras protein signal transduction (GO: 0007265), and conta

251 Ras proteins signal through direct interaction with a nu

252 Ras proteins signal to a number of distinct pathways by

253 we initially hypothesized a role for active Ras protein signaling in exosome biogenesis, we found th

254 t-negative or an S-nitrosylation-site mutant Ras protein significantly abrogates the effects of NO.

255 Expression of a dominant-negative Ras protein significantly inhibited MMP-2 transcription,

256 hearts arose from up-regulated expression of Ras protein-specific guanine nucleotide releasing factor

257 At Rasgrf1 (encoding RAS protein-specific guanine nucleotide-releasing factor

258 e kinase, mitochondrial 2) and RASGRF2 gene (Ras protein-specific guanine nucleotide-releasing factor

259 impairs the ability of CARD9 to complex with Ras protein-specific guanine nucleotide-releasing factor

260 The p21 Ras proteins, such as K-Ras4B, K-Ras4A, H-Ras, and N-Ras

261 familiar farnesylated proteins belong to the Ras protein superfamily, well-known oncoproteins.

262 ll mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promo

263 neated a unique ligand-binding pocket on the Ras protein that is adjacent to the switch I/II regions

264 ory nucleotide analogues, respectively, of K-Ras proteins that covalently and selectively bind G12C-m

265 nd reveal unexpected plasticity in oncogenic Ras proteins that has diagnostic and therapeutic implica

266 , resulting in mixed heterotypic clusters of Ras proteins that normally are separated spatially.

267 wo well-studied examples, Gpa1 and the human RAS proteins, that have revealed additional mechanisms o

268 ate cellular transformation by the classical Ras proteins, the mechanisms through which TC21 induces

269 views the properties of normal and oncogenic Ras proteins, the prevalence and likely pathogenic role

270 ng proteins inhibit RAS activity and deplete RAS proteins through an autophagosome-lysosome-mediated

271 Nf1 and examined mice doubly deficient in a Ras protein to determine its requirement in formation of

272 e endomembrane and that in order for a given Ras protein to fully transform cells, multiple compartme

273 l modifications of all RAS HVRs helps target RAS proteins to cellular membrane locations where they p

274 tiation, and survival signals from activated RAS proteins to downstream effectors, most often by indu

275 that efficient cell transformation requires Ras proteins to interact with Cdc42 on the endomembrane

276 nase as well as for the correct targeting of Ras proteins to lipid rafts and non-raft membranes.

277 in accelerates KRAS prenylation and requires RAS proteins to promote cell proliferation.

278 Subcellular localization of Ras proteins to the plasma membrane is accomplished in p

279 C-terminal targeting sequences or the entire Ras proteins to Venus fluorescent protein.

280 Ras proteins traffic between the plasma membrane and end

281 Ras proteins transduce extracellular signals to intracel

282 Oncogenic Ras proteins transform cells via multiple downstream sig

283 Activation of Ras proteins underlies functional decisions in diverse c

284 compound, termed 3144, was found to bind to RAS proteins using microscale thermophoresis, nuclear ma

285 Redistribution of the two Ras proteins was monitored with confocal microscopy or w

286 ng in erythroid differentiation, different H-ras proteins were expressed in CFU-E progenitors and ear

287 In MEFs lacking Rce1 or Icmt, farnesylated Ras proteins were mislocalized.

288 t heterologously expressing mammalian mutant Ras proteins were used to immunize mice in a carcinogen-

289 es, KRAS, NRAS, and HRAS, encode 4 different RAS proteins which belong to the protein family of small

290 Common substrates include oncogenic Ras proteins, which are implicated in up to 30% of all h

291 Oncogenic RAS proteins, which are mutated in approximately 24% of

292 study, we demonstrate that unlike oncogenic Ras proteins, which are primarily activated by mutations

293 ation and activation of endogenous wild-type Ras proteins, which are required throughout tumorigenesi

294 However, the specific Ras proteins, which integrate in vivo with TGF-beta sign

295 Ras proteins-which are activated by many upstream pathwa

296 show that RasDM is the first structure of a Ras protein with identical GDP- and GTP-bound structures

297 We find that C-Raf binds all mutant Ras proteins with high affinity, whereas B-Raf exhibits

298 Directly targeting Ras proteins with small molecules may rely on the moveme

299 Remarkably, K-Ras proteins with switch 2 insertions are impaired for P

300 nds capable of inhibiting the interaction of RAS proteins with their effectors that transduce the sig