ライフサイエンスコーパス: c-Cbl

1 emonstrated an association of 5-HT(2A)R with c-Cbl.

2 iRNA knockdown, but enhanced by knockdown of c-Cbl.

3 trong Vav1 signals to overcome inhibition by c-Cbl.

4 Ring finger domain mutant functions like WT c-Cbl.

5 itination of the EGFR and the recruitment of c-Cbl.

6 RING domain and in T cells from mice lacking c-Cbl.

7 by eliminating negative effects mediated by c-Cbl.

8 mapped the membrane interactive domain(s) of c-Cbl.

9 ase activity or its ability to interact with c-Cbl.

10 tol-3-kinase (PI3K) with membrane-associated c-Cbl.

11 to c-Kit(hi) HSC is negatively regulated by c-Cbl.

12 which prevents the ubiquitination of Nck1 by c-Cbl.

13 ype c-Cbl suppresses and E3 ligase-deficient c-Cbl-70Z increases Wnt signaling.

14 the inhibitory signal transduction proteins, c-Cbl, a ubiquitin-ligase (p < .01) and SHP-1, a phospha

15 sitive endosomes, where activated PAR(2) and c-Cbl accumulated, and PAR(2) failed to traffic to lysos

16 This Cbl-b (and c-Cbl) accumulation at the anergic synapse may play an i

17 c-Cbl activation also inhibits expression of the pro-ang

18 Cat.G treatment induced c-Cbl activation and its interaction with FA proteins.

19 Interestingly, c-Cbl activation induced by Cat.G was mediated through e

20 c-Cbl activation promotes myocyte apoptosis, inhibits an

21 c-Cbl activity inhibits pro-angiogenic Wnt targets IL-8

22 of signaling complexes upon TCR stimulation, c-Cbl activity is involved in the internalization and po

23 angiogenesis, suggesting that modulation of c-Cbl activity or inhibition of PLCgamma1 would be a com

24 dependent, it is complexed with the Gab2 and c-Cbl adapter/scaffold proteins, and it mediates persist

25 e shown that the Casitas b-lineage lymphoma (c-Cbl), adaptor protein with an intrinsic E3 ubiquitin l

26 ion preferences of its three SH3 domains for c-CBL, ALIX, and RIN3.

27 Loss of c-Cbl also resulted in robust activation of PLCgamma1 an

28 Pkd1-null cells, Casitas B-lineage lymphoma (c-Cbl), an E3-ubiquitin ligase for c-Met, was sequestere

29 to identification of homozygous mutations in c-Cbl, an E3 ubiquitin ligase involved in attenuation of

30 ificant reduction in the expression level of c-Cbl, an E3 ubiquitin ligase that ubiquitinylates PDGFR

31 nylating enzyme, siRNA-mediated knockdown of c-Cbl, an E3 ubiquitin ligase, abolished the arsenic-sti

32 lly, increased interaction between GCase and c-Cbl, an E3 ubiquitin ligase, may be involved in the de

33 coprecipitates with the E3 ubiquitin ligase c-Cbl and also with the deubiquitinating enzyme USP9x; m

34 ced differentiation can thus be propelled by c-Cbl and by CD38, both of which bind together, enhance

35 (IFT20) interacts with E3 ubiquitin ligases c-Cbl and Cbl-b and is required for Cbl-mediated ubiquit

36 c-Cbl and Cbl-b are highly conserved adaptor proteins th

37 We identified c-Cbl and Cbl-b as proteins that undergo tyrosine phosph

38 nding domain bound to beta-tubulin, and both c-Cbl and Cbl-b displaced HDAC6.

39 In summary, novel mutations in c-CBL and CBL-b have been identified in human AML and ma

40 Deletion of both c-Cbl and Cbl-b in mice leads to embryonic lethality, in

41 To examine the redundant actions of c-Cbl and Cbl-b in osteoclasts, we depleted c-Cbl in Cbl

42 Depletion of c-Cbl and Cbl-b led to an increased ligand-induced tyros

43 Thus, both c-Cbl and Cbl-b promote bone resorption via the stabiliz

44 Simultaneous depletion of c-Cbl and Cbl-b resulted in reduced ligand-induced PDGFR

45 striking, there was specific accumulation of c-Cbl and Cbl-b to the anergic synapses.

46 ubiquitinated in a manner requiring both the c-Cbl and Cbl-b ubiquitin ligases.

47 unctionally, we found that cells depleted of c-Cbl and Cbl-b were more prone to migrate toward PDGF-B

48 Indeed, in cells depleted of c-Cbl and Cbl-b, both Src and PLCgamma phosphorylation w

49 e two known Syk-binding E3 ubiquitin ligases c-Cbl and Cbl-b, only c-Cbl appears to have a central ro

50 activity, was also elevated in cells lacking c-Cbl and Cbl-b.

51 ecause of destabilization and degradation of c-Cbl and Cbl-b.

52 ansfer and coimmunoprecipitation showed that c-Cbl and CD38 bind each other.

53 here thus seems to be a cooperative role for c-Cbl and CD38, reflected in their direct binding, in pr

54 t with RA, suggesting an interaction between c-Cbl and CD38.

55 H-Ras interacts with Spry2-binding partners, c-Cbl and CIN85, in a Spry2-dependent manner.

56 dation by binding to the E3 ubiquitin ligase c-Cbl and decreasing the ubiquitination of EGFR.

57 the interaction between the adapter protein c-Cbl and EGFR, but not the phosphorylation state of EGF

58 scovery of tumor suppressor genes, including c-CBL and family members, as well as TET2.

59 Y1045 and Y1068, the known docking sites of c-Cbl and Grb2, respectively, whereas promoting phosphor

60 Y2-mediated regulation of apoptosis requires c-Cbl and is manifested by the ability of hSPRY2 to sequ

61 ffects on other E3 ubiquitin ligases such as c-Cbl and Itch.

62 regulation of active nuclear beta-catenin by c-Cbl and its critical role in angiogenesis.

63 sphorylation at residues targeted by Src and c-cbl and leads to increased surface exposure of EGFR by

64 studies suggest that interventions targeting c-Cbl and LRs are potential avenues to block KSHV infect

65 These results indicate that c-Cbl and particularly its phosphorylated residue Y731 p

66 Our data demonstrate that corecruitment of c-Cbl and PLCgamma1 to VEGFR-2 serves as a mechanism to

67 c-Cbl and RAS pathway mutations were mutually exclusive.

68 ng inhibitors of the EGFR pathway, including c-Cbl and RasGAP, and more than that of MAPK phosphatase

69 n CREB were also simultaneously depressed as c-Cbl and SHP-1 were elevated.

70 The interaction between c-Cbl and SLAP in v-Abl-3T3 cells positively influenced

71 x recycling depended on enzymatically active c-Cbl and Src family kinases, as well as the intact SH2

72 gulation of c-MPL signaling by the E3 ligase c-CBL and the cholesterol-sensing LYN kinase.

73 fested by the ability of hSPRY2 to sequester c-Cbl and thereby augment signaling via growth factor re

74 with transient association of the EGFR with c-Cbl and transient EGFR ubiquitination.

75 eceptor signaling (Sts)-2 is associated with c-Cbl and ubiquitylated proteins and has been implicated

76 The physiologic role of c-Cbl and Y731 was studied using platelets from c-Cbl KO

77 se kinase (MEK), Casitas B-lineage lymphoma (c-Cbl), and the pro-oncogene Src activity.

78 nt pathways that are negatively regulated by c-Cbl, and further suggest that different events during

79 , resulting in the lack of ubiquitination by c-Cbl, and impaired degradation.

80 tion, recruitment of the E3 ubiquitin ligase c-Cbl, and rapid intracellular degradation of Met (half-

81 FAK), Src, phosphoinositol 3-kinase (PI3-K), c-Cbl, and RhoA GTPase signal molecules early during lip

82 he CD3varepsilon proline-rich sequence, Lck, c-Cbl, and SLAP, which collectively trigger the dynamin-

83 g E3 ubiquitin ligases c-Cbl and Cbl-b, only c-Cbl appears to have a central role in BCR ubiquitinati

84 In previous study we have identified c-Cbl as a negative regulator of PLCgamma1 in endothelia

85 In essence, our data unequivocally identify c-Cbl as a novel negative regulator of developmental and

86 These findings point to c-Cbl as a potential therapeutic target for the maintena

87 ations in subsets of myeloid cancer and (ii) c-Cbl as a prostate basal cell marker that correlates wi

88 This study defines for the first time c-Cbl as a ubiquitin E3 ligase that targets nuclearly ac

89 Hence, we propose c-Cbl as an angiogenic suppressor protein where upon act

90 Cbl-b formed a complex with c-Cbl, as well as with the PDGFRbeta, in response to PDG

91 brane microdomains, via the adapter protein, c-Cbl associated protein (CAP).

92 t activation promotes the phosphorylation of c-Cbl at tyrosine 731(Tyr-731), which increases c-Cbl di

93 In wild-type cells treated with PDGF-AA, c-Cbl becomes enriched in the cilium, and the receptor i

94 osphorylation at the autophosphorylation and c-Cbl binding sites in mouse xenografts derived from non

95 sed EGFR autophosphorylation on the Grb2 and c-Cbl-binding sites correlated with receptor stability a

96 c-Cbl binds preferentially to nuclearly active beta-cate

97 This is consistent with the finding that c-Cbl binds specifically to the Ras GAP domain.

98 acid transporter x-CT protein and enters via c-Cbl-bleb-mediated macropinocytosis.

99 NK(-/-) pre-BCR(+) pre-B cells compared with c-Cbl(+/-)BLNK(-/-) cells, including elevated phosphoryl

100 c-Cbl(-/-)BLNK(-/-) mice exhibited normalized down-regul

101 ed and prolonged tyrosine phosphorylation in c-Cbl(-/-)BLNK(-/-) pre-BCR(+) pre-B cells compared with

102 b is expressed in human platelets along with c-Cbl, but in contrast to c-Cbl, it is not tyrosine-phos

103 sphorylated tyrosine residue at codon 774 of c-Cbl, but is also essential for the tumorigenicity obse

104 Furthermore, down-regulation of c-Cbl by RNA interference blocked efficient recycling of

105 Silencing of c-Cbl by siRNA revealed that endogenous c-Cbl plays an i

106 atively regulated by the E3 ubiquitin ligase c-Cbl (casitas B-cell lymphoma).

107 Several human c-Cbl (CBL) structures have recently been solved, depict

108 serum, the tyrosine kinase binding domain of c-Cbl (Cbl-TKB) protected against down-regulation of the

109 We sequenced c-Cbl, Cbl-b, and Cbl-c in patients with or without corr

110 Several E3 ubiquitin ligases, including c-Cbl, Cbl-b, GRAIL, Itch, and Nedd4, have been shown to

111 c-Cbl co-immunoprecipitated with CFTR in primary differe

112 Moreover, CFTR and c-Cbl co-localized and co-immunoprecipitated in early en

113 The G306E mutant does, like WT c-Cbl, co-immunoprecipitate with Vav, Slp-76, and p38.

114 teractor Casitas B-lineage lymphoma protein (c-CBL), conducted a peptide array screen based on the re

115 c-Cbl-deficient macrophages expressed less Fc gammaRIIb,

116 In c-Cbl-deficient macrophages, CSF-1R ubiquitination and t

117 c-Cbl-deficient mice demonstrated a more robust function

118 c-Cbl-deficient mice show normal frequencies of lymphocy

119 Interestingly, c-Cbl deletion reduced the risk of death and increased c

120 This beneficial effect of c-Cbl deletion was associated with enhanced neoangiogene

121 c-Cbl-dependent ubiquitination selectively inhibited tyr

122 Silencing c-Cbl did not change the expression of the ubiquitinated

123 bl at tyrosine 731(Tyr-731), which increases c-Cbl dimerization and binding to beta-catenin.

124 nd-binding results in phosphorylation of the c-Cbl docking tyrosine and ubiquitination of the recepto

125 But unlike WT c-Cbl, does not cause MAPK signaling.

126 We therefore investigated the role of c-Cbl during B cell development and addressed the possib

127 Acquired mutations of c-Cbl E3 ubiquitin ligase may explain the pathogenesis o

128 we show that the Casitas B-lineage lymphoma (c-Cbl) E3 ubiquitin ligase constitutively associates wit

129 s inability to bind the E3 ubiquitin ligase, c-Cbl, either directly or indirectly via the Grb2 adapte

130 Transfection of WT c-Cbl enhanced EGFR degradation and cisplatin-induced cy

131 We show increased c-Cbl expression in human ischemic and dilated cardiomyo

132 Inhibition of c-Cbl expression or its ubiquitin ligase activity in car

133 lls ectopically expressing CD38 had enhanced c-Cbl expression, even without with RA, suggesting an in

134 gradual down-regulation and eventual loss of c-Cbl expression, resulting in loss of the Cbl-CD38 inte

135 We had previously reported that c-Cbl facilitates cell spreading and adhesion and suppre

136 nlike wild-type (WT) c-Cbl, the G306E mutant c-Cbl fails to propel RA-induced differentiation, and di

137 biquitin ligase, Casitas B-lineage lymphoma (c-Cbl), followed by ubiquitination in the relatively cis

138 We now find that synaptopodin competes with c-Cbl for binding to Nck1, which prevents the ubiquitina

139 s the importance of membrane localization of c-Cbl for the observed effects of c-Cbl in v-Abl-3T3 cel

140 stent with a model in which the G306E mutant c-Cbl forms a signaling complex that includes Slp-76, Va

141 pared with that observed for the full-length c-Cbl fusion protein.

142 Cells ectopically expressing c-Cbl had enhanced CD38 expression when treated with RA,

143 Here, we identify c-Cbl (henceforth referred to as Cbl) as a GM-CSF recept

144 e biochemical and biological significance of c-Cbl, however, in angiogenesis in vivo and molecular me

145 Our mechanistic studies identified that c-Cbl(-/-) HSCs are hyperresponsive to thrombopoietin (T

146 2 (SRSF2), p53, casitas B-lineage lymphoma (c-CBL), ikaros zinc fingers (IKZF), neurofibromin 1 (NF1

147 ied missense mutations in the proto-oncogene c-Cbl in 7 of 12 patients with UPD11q.

148 c-Cbl and Cbl-b in osteoclasts, we depleted c-Cbl in Cbl-b(-/-) osteoclasts by using a short hairpin

149 endent increase in serine phosphorylation of c-Cbl in cells expressing elevated levels of CD82.

150 to evaluate the importance of PLCgamma1 and c-Cbl in experimental choroidal neovascularization (CNV)

151 that a deficiency of the E3 ubiquitin ligase c-Cbl in lymphocytes results in an age-dependent lymphop

152 These data support novel functions of c-Cbl in mediating recycling of EGF receptors to the pla

153 tudy, we report that genetic inactivation of c-Cbl in mice results in enhanced tumor angiogenesis and

154 In this study, we examined the role of c-Cbl in myocyte death and cardiac function after myocar

155 ng the importance of the E3 ubiquitin ligase c-Cbl in rapid down-regulation of Tpo/Mpl signaling.

156 nting a global role for the ubiquitin ligase c-Cbl in regulating vesicular sorting of epidermal growt

157 gnaling and the Syk-binding ubiquitin ligase c-Cbl in the BCR-mediated processing and presentation of

158 However, the function of c-Cbl in the control of cardiac function is currently un

159 fects not simply by increasing the amount of c-Cbl in the membrane but by facilitating binding of p85

160 Ralpha and have unraveled the involvement of c-Cbl in the ubiquitylation of IL7Ralpha.

161 ization of c-Cbl for the observed effects of c-Cbl in v-Abl-3T3 cells, we first mapped the membrane i

162 d these responses, while expression of C381A c-Cbl in wild-type macrophages suppressed them.

163 uitin E3 ligase, Casitas B-lineage lymphoma (c-Cbl) in endothelial cells.

164 c-Cbl inactivation also reversed the potentially tumor-p

165 Strikingly, c-Cbl inactivation reversed a number of the critical def

166 Small interfering RNA-mediated silencing of c-Cbl increased CFTR expression in the plasma membrane b

167 arly during infection (1 min postinfection), c-Cbl induced the selective translocation of KSHV into t

168 Interestingly, Spry2 also prevents the c-Cbl-induced degradation of epidermal growth factor rec

169 c-Cbl inhibited Vav1-dependent signals, given that c-Cbl

170 in which neutrophil protease Cat.G promotes c-Cbl interaction with FA proteins, resulting in enhance

171 c-Cbl is a multifunctional molecule with ubiquitin ligas

172 The multi-functional protein c-Cbl is an important modulator of actin cytoskeletal dy

173 ac-Cbl dominant negative mutant to show that c-Cbl is critical for the efficient transition of the EG

174 mily kinase (SFK) inhibitor, suggesting that c-Cbl is phosphorylated downstream of SFKs.

175 e proto-oncogene Casitas b-lineage lymphoma (c-Cbl) is an adaptor protein with an intrinsic E3 ubiqui

176 Cbl-b, unlike c-Cbl, is not required for Syk ubiquitylation downstream

177 eport, we show that the E3 ubiquitin ligase, c-CBL, is overexpressed in CTCL and that its knockdown o

178 atelets along with c-Cbl, but in contrast to c-Cbl, it is not tyrosine-phosphorylated upon glycoprote

179 Deletion of c-Cbl using c-Cbl knock-out derived myocytes or inhibition of c-Cbl

180 Moreover, c-Cbl knockdown and Vav1 overexpression each circumvente

181 c-Cbl knockdown blocked the macropinocytosis and recepto

182 inhibited Vav1-dependent signals, given that c-Cbl knockdown did not rescue the Vav1 defect.

183 In contrast, c-Cbl knockdown stable transfectants differentiated slow

184 nant over synergistic activation, even after c-Cbl knockdown.

185 hesion kinase, were significantly reduced in c-Cbl knockout mice.

186 CNV lesions in the c-Cbl-knockout mice were significantly greater in number

187 CNV was induced in wild-type and c-Cbl-knockout mice, and the progression of CNV was eval

188 bl and Y731 was studied using platelets from c-Cbl KO and c-Cbl(YF/YF) knock-in mice.

189 c-Cbl KO and c-Cbl(YF/YF) platelets had a significantly

190 Furthermore, clot retraction with c-Cbl KO and c-Cbl(YF/YF) platelets was drastically dela

191 knock-out derived myocytes or inhibition of c-Cbl ligase activity significantly reduced FA protein d

192 Activated c-Cbl localized with LRs at the junctional base of macro

193 Our results indicate that mutations in c-Cbl may represent key molecular lesions in JMML patien

194 action with nuclear beta-catenin, leading to c-Cbl mediated degradation of beta-catenin, and conseque

195 n the CSF-1R further suggests that activated c-Cbl-mediated CSF-1R ubiquitination is required for a c

196 1045F EGFR, which is relatively resistant to c-Cbl-mediated degradation, in Chinese hamster ovary cel

197 tion with FA proteins, resulting in enhanced c-Cbl-mediated FA protein ubiquitination and degradation

198 LAP in v-Abl-3T3 cells positively influenced c-Cbl-mediated spreading and adhesion of these cells.

199 w that Nck1, but not Nck2, is a substrate of c-Cbl-mediated ubiquitination.

200 HSCs of c-Cbl(-/-) mice exhibit augmented pool size, hyperprolif

201 Thus, we tested the hypothesis that c-Cbl might play a role in 5-HT(2A)R recycling.

202 that a lack of signaling events mediated by c-Cbl might result in diminished lymphocyte development

203 Intriguingly, c-Cbl mutant lymphocytes displayed increased responses t

204 Moreover, the c-Cbl mutant with impaired ubiquitin ligase activity (FL

205 In contrast, the c-Cbl mutant with the truncated C-terminal region (FLAG-

206 on was greatly attenuated in the presence of c-Cbl mutants lacking carboxyl termini, as detected by c

207 ve sorting endosomes in cells overexpressing c-Cbl mutants lacking carboxyl termini.

208 expressing versions of the ubiquitin ligase c-Cbl mutated in the RING domain and in T cells from mic

209 Each c-CBL mutation involves the structurally important alpha

210 Serial studies showed acquisition of c-Cbl mutations during malignant evolution.

211 We identified c-Cbl mutations in 5% and 9% of patients with chronic my

212 s the identification of (i) gain of function c-Cbl mutations in subsets of myeloid cancer and (ii) c-

213 In total, c-Cbl mutations were detected in 5 (10%) of 49 patients.

214 patients and the MOLM-13 cell line harbored c-CBL mutations, either RNA splicing mutations, missense

215 potent therapy indicating that patients with c-Cbl mutations, or those with similarly enhanced Flt3 s

216 d lower hemoglobin F levels in patients with c-Cbl mutations.

217 l of these cases harbored RING finger domain c-Cbl mutations.

218 Most mutations were homozygous and affected c-Cbl; mutations in Cbl-b were also found in patients wi

219 EphA2 associates with c-Cbl-myosin IIA and augmented KSHV-induced Src and PI3-

220 731 phosphorylation and dimerization mediate c-Cbl nuclear translocation and lead to the degradation

221 zation, binding to beta-catenin, Wnt-induced c-Cbl nuclear translocation, and ubiquitination of nucle

222 Additionally, silencing of Spry2 in c-Cbl null cells did not alter the ability of serum to p

223 Endothelial cells derived from c-Cbl null mice displayed elevated cell proliferation an

224 hSPRY2, but not its mutants that do not bind c-Cbl or CIN85 into SW13 cells after endogenous hSPRY2 h

225 receptor dimerization leads to a Tyr-559/SFK/c-Cbl pathway resulting in receptor ubiquitination that

226 es such as focal adhesion kinase (FAK), Src, c-Cbl, phosphoinositide 3-kinase (PI-3K), and Rho-GTPase

227 of EGFR kinase activity markedly attenuated c-Cbl phosphorylation and FA protein degradation induced

228 SI-2, a Syk inhibitor, significantly reduced c-Cbl phosphorylation at residues Y774 and Y700, without

229 ibiting formation of a Src Family Kinase SFK.c-Cbl.PI3K complex and the downstream activation of Vav3

230 the discovery that the C-terminal region of c-Cbl plays a crucial role in the temporal and spatial c

231 of the Cbl-CD38 interaction, suggesting that c-Cbl plays a relatively early role in promoting RA-indu

232 The study also shows that c-Cbl plays an important role in ocular angiogenesis, su

233 g of c-Cbl by siRNA revealed that endogenous c-Cbl plays an inhibitory role in angiogenesis.

234 emination of ExoT-producing bacteria whereas c-Cbl plays no detectable role.

235 Another adaptor protein, c-Cbl, plays a negative regulatory role in several BCR-s

236 Short-interfering RNA knockdown of mutant c-CBL present in MOLM-13 cells was growth inhibitory.

237 emonstrated that Casitas B-lineage lymphoma (c-Cbl) promotes ubiquitination of PLCgamma1 and suppress

238 c-Cbl protein functions as an E3 ligase and scaffolding

239 fects correlated with impaired activation of c-Cbl, Pyk2, Erk1/2, and p38 kinases.

240 direct interaction between the receptor and c-Cbl, raising the possibility that Cbl-b is necessary f

241 ecipitated in early endosomes, and silencing c-Cbl reduced the amount of ubiquitinated CFTR in early

242 trate that in human airway epithelial cells, c-Cbl regulates CFTR by two mechanisms: first by acting

243 hese studies provide the first evidence that c-Cbl regulates selective KSHV-alpha3beta1, -alphaVbeta3

244 ly endosomes to a recycling pathway and that c-Cbl regulates the duration of extracellular signal reg

245 nown about the molecular mechanisms by which c-Cbl regulates ubiquitination and degradation of active

246 is of VEGFR-2 showed that full activation of c-Cbl requires its direct association with phospho-tyros

247 pe, but not ubiquitin ligase-defective C381A c-Cbl rescued these responses, while expression of C381A

248 Similarly, expression of c-Cbl-resistant Nck1(K178R) or Nck2 containing the SH3 d

249 Gene silencing of c-Cbl restores Nck1 protein abundance and stress fibres

250 Loss of c-Cbl results in enhanced CNV in the eye.

251 Using the c-Cbl RING finger mutant mouse as a model of a myeloprol

252 Moreover, c-Cbl RING mutant forms suppressed LAT ubiquitylation an

253 ated that the conserved four-helix bundle of c-Cbl's tyrosine kinase binding domain bound to beta-tub

254 lex formation between VEGFR-2, PLCgamma1 and c-Cbl selectively promotes ubiquitylation and suppressio

255 binds CD38 and is part of the same apparent c-Cbl/Slp-76/Vav/p38 signaling complex.

256 Most importantly, we used c-Cbl small interfering RNA (siRNA) duplexes and ac-Cbl

257 Lyn also negatively regulates c-Cbl stability, whereas c-Cbl tyrosine phosphorylation

258 s its interaction with and ubiquitination by c-CBL, stabilizing it and augmenting activation of itsel

259 dition to HL-60 cells and their WT or mutant c-Cbl stable transfectants, the c-Cbl/Vav/Slp-76 complex

260 Wild-type c-Cbl suppresses and E3 ligase-deficient c-Cbl-70Z incre

261 itination and downregulation of key survival c-Cbl targets, epidermal growth factor receptors and foc

262 fMLP induced phosphorylation of c-Cbl that was sustained for at least 45 min.

263 Unlike wild-type (WT) c-Cbl, the G306E mutant c-Cbl fails to propel RA-induced

264 Here we report that the capability of c-Cbl to do this is lost in the G306E tyrosine kinase-bi

265 the possibility that Cbl-b is necessary for c-Cbl to interact with PDGFRbeta.

266 cess, partly because of increased binding of c-Cbl to p85beta relative to p85alpha.

267 ance of the Gly306 residue in the ability of c-Cbl to propel RA-induced differentiation.

268 Our studies indicate that localization of c-Cbl to the membrane is likely to be mediated by the ty

269 d with a relative decrease in association of c-Cbl truncation proteins with the 5-HT(2A)R, compared w

270 y and sufficient for these responses and for c-Cbl tyrosine phosphorylation and all three responses w

271 egatively regulates c-Cbl stability, whereas c-Cbl tyrosine phosphorylation is mediated by BCR-ABL.

272 Deletion of the c-Cbl UBA domain abrogates its dimerization, binding to

273 ave been shown to effectively induce initial c-Cbl (ubiquitin ligase)-mediated ubiquitination of the

274 The E3 ligase c-Cbl ubiquitinates protease-activated receptor 2 (PAR(2

275 The E3 ubiquitin ligase c-Cbl ubiquitinates the G protein-coupled receptor prote

276 Stable transfectants ectopically expressing c-Cbl underwent myeloid differentiation faster than wild

277 Without the G306E mutation the c-Cbl unites CD38 with the signaling complex and deliver

278 Deletion of c-Cbl using c-Cbl knock-out derived myocytes or inhibiti

279 WT or mutant c-Cbl stable transfectants, the c-Cbl/Vav/Slp-76 complex is also found in NB4 cells wher

280 phosphorylation and increased expression of c-Cbl, Vav1, and the Src-family kinases (SFKs) Lyn and F

281 Recently, c-Cbl was identified as a unique E3 ubiquitin ligase tar

282 Phosphorylation of c-Cbl was inhibited by a Syk kinase inhibitor but with a

283 -76 complex is also found in NB4 cells where c-Cbl was previously also found to bind CD38.

284 LRA-2 resulted in phosphorylation of Syk and c-Cbl, was inhibited by a third generation Syk inhibitor

285 Wnt induces nuclear translocation of c-Cbl where it ubiquitinates nuclear beta-catenin.

286 (TKB) domain and the proline-rich region of c-Cbl, whereas C-terminal tyrosine phosphorylation does

287 The process is propelled by c-Cbl, which binds the CD38 receptor as part of a signal

288 Our data identify CD82 as a new regulator of c-Cbl, which discriminatively controls the activity of t

289 adation of CFTR by increasing phosphorylated c-Cbl, which increased its interaction with CFTR, and su

290 KSHV infection activated c-Cbl, which induced the selective translocation of KSHV

291 negative overexpression, we also found that c-Cbl, which is activated by Tpo, acts as an E3 ubiquiti

292 al studies have identified an interaction of c-Cbl with IL7Ralpha and have unraveled the involvement

293 Further analysis showed that association of c-Cbl with VEGFR-2 does not impact ubiquitylation, down-

294 We observed that c-Cbl Y700, Y731 and Y774 undergo phosphorylation upon p

295 l (Y731F) enhances and phosphomimetic mutant c-Cbl (Y731E) suppresses angiogenesis in zebrafish.

296 Phospho-Tyr-731-inactive mutant c-Cbl (Y731F) enhances and phosphomimetic mutant c-Cbl (

297 as studied using platelets from c-Cbl KO and c-Cbl(YF/YF) knock-in mice.

298 c-Cbl KO and c-Cbl(YF/YF) platelets had a significantly reduced sprea

299 rthermore, clot retraction with c-Cbl KO and c-Cbl(YF/YF) platelets was drastically delayed.

300 (ZAP-70-KA(369)), or a ZAP-70 unable to bind c-Cbl (ZAP-YF(292)) experienced greater intracellular ca