ライフサイエンスコーパス: c-Cbl

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

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

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

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

5 of HER2 by the proteasome via the E3 ligase c-CBL.

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

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

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

9 ng antibody suggesting regulation of PD-1 by c-Cbl.

10 by eliminating negative effects mediated by c-Cbl.

11 gradation of mTOR by the E3 ubiquitin ligase c-Cbl.

12 to c-Kit(hi) HSC is negatively regulated 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 This Cbl-b (and c-Cbl) accumulation at the anergic synapse may play an i

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

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

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

19 c-Cbl activation promotes myocyte apoptosis, inhibits an

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

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

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

23 c-CBL acts as a coordinator in this complex enabling CD5

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 In contrast, haploinsufficiency of c-Cbl(+/-) alone was insufficient to induce tumorigenesi

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

29 Here we demonstrate that c-Cbl alters the tumor microenvironment and suppresses P

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 Mast cells, however, express little c-Cbl and have correspondingly high LynA.

61 o demonstrates that combined partial loss of c-Cbl and inactivation of APC significantly contribute t

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

87 This data demonstrates c-Cbl as an E3 ligase of PD-1 and a regulator of tumor m

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

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

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

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

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

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

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

95 Advancing immune checkpoint and c-Cbl biology, our study prompts for probing of PD-1 reg

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

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

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

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

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

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

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

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

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

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

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

107 ng site for proteins with adaptor functions (c-Cbl, CIN85, CRKL), connecting CD5 to positive (PI3K) a

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

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

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

111 xenografts and infiltrating immune cells in c-Cbl(+/-) compared to c-Cbl(+/+) mice.

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

113 C(Delta14/+) c-Cbl(+/+) mice, APC(Delta14/+) c-Cbl(+/-) crypts showed nuclear beta-catenin throughout

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

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

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

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

118 tivation of mTOR expression and signaling in c-Cbl-deficient MPs results in increased mature myeloid

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 c-Cbl destabilized PD-1 through ubiquitination- proteaso

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

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

125 Haploinsufficient c-Cbl mice (APC(Delta14/+) c-Cbl(+/-)) displayed a significant (threefold) increase

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

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

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

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

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

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

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

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

134 Cell-specific c-Cbl expression thus builds cell specificity into the L

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

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

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

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

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

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 We hypothesized that reduction in c-Cbl in colonic epithelium is likely to increase the le

151 dy prompts for probing of PD-1 regulation by c-Cbl in conditions driven by immune checkpoint abnormal

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

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

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

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

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

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

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

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

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

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

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

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

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

167 hanistic probing revealed that C-terminus of c-Cbl interacted with the cytoplasmic tail of PD-1.

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

169 c-Cbl is a multifunctional molecule with ubiquitin ligas

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

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

172 Casitas B-lineage lymphoma (c-Cbl) is a recently identified ubiquitin ligase of nucl

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

174 Casitas B lymphoma (c-Cbl) is an E3 ubiquitin ligase and a negative regulato

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

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

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

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

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

180 c-Cbl knockdown blocked the macropinocytosis and recepto

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

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

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

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

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

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

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

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

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

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

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

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

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

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

195 1045F EGFR, which is relatively resistant to c-Cbl-mediated degradation, in Chinese hamster ovary cel

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

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

198 Haploinsufficient c-Cbl mice (APC(Delta14/+) c-Cbl(+/-)) displayed a signi

199 In contrast to the APC(Delta14/+) c-Cbl(+/+) mice, APC(Delta14/+) c-Cbl(+/-) crypts showed

200 ating immune cells in c-Cbl(+/-) compared to c-Cbl(+/+) mice.

201 ciated CD8+ T-lymphocytes and macrophages of c-Cbl(+/-) mice showed 2-3-fold higher levels of PD-1.

202 Functionally, macrophages from c-Cbl(+/-) mice showed a 4-5-fold reduction in tumor pha

203 d SRY-box transcription factor 9 in APC(+/+) c-Cbl(+/-) mice.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

222 731 phosphorylation and dimerization mediate c-Cbl nuclear translocation and lead to the degradation

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

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

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

226 gh expression in immune cells, the effect of c-Cbl on the tumor microenvironment remains poorly under

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

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

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

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

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

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

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

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

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

236 lyses, we found that the E3 ubiquitin ligase c-Cbl preferentially targets LynA via a phosphorylated t

237 he binding of AXL to the Cbl proto-oncogene (c-Cbl); promoted AXL ubiquitination; decreased AXL-media

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

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

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

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

242 This distinct mode of c-Cbl recognition depresses steady-state expression of L

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

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

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

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

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

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

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

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

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

252 tudy demonstrates that haploinsufficiency of c-Cbl results in Wnt hyperactivation in intestinal crypt

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

254 nation- proteasomal degradation depending on c-Cbl's RING finger function.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

284 -76 complex is also found in NB4 cells where c-Cbl was previously also found to bind CD38.

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

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

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

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

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

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

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

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

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

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