ライフサイエンスコーパス: Btk

1 Btk and Csk function downstream of phosphatidylinositol

2 Btk appears to regulate directly the classical pathway i

3 Btk deficiency reduced Notch2(+/-) signaling exclusively

4 Btk has been demonstrated to regulate signaling downstre

5 Btk is essential for B-cell receptor signaling, because

6 Btk is required for pre-B cell clonal expansion and B-ce

7 Btk plays crucial roles in the differentiation and activ

8 Btk-deficient bone marrow-derived macrophages secrete de

9 Btk-deficient mice exhibit decreased serum IgM productio

10 Btk-PH and TAPP1-PH showed genuine PtdIns(3,4,5)P3 and P

11 Using xid mice and a Btk inhibitor, we show that BCR engagement increases act

12 e further provide evidence that ibrutinib, a Btk inhibitor that promotes mobilization of leukemic cel

13 ion are enhanced in SHIP-1(-/-) B cells in a Btk-dependent manner.

14 ott-Aldrich syndrome protein activation in a Btk-dependent manner.

15 nts, Ets1 levels are reduced in B cells in a Btk-dependent manner.

16 BTK transgenic mice were bred onto a Btk knockout background to avoid interference of the ort

17 NMR titration experiments using a Btk (Bruton's tyrosine kinase) kinase domain as a surrog

18 results suggest that PU.1 and Spi-B activate Btk to oppose IL-7 responsiveness in developing B cells.

19 both animal and plant cells, also activates Btk.

20 In addition, Btk-deficient B cells produce reduced levels of NF-kappa

21 t restored pS6 to wild-type levels, although Btk protein and phosphorylation levels were comparable t

22 rounds (recombinase-activating gene 2-/- and Btk-/- Tec-/-) whereby B cell development is arrested, w

23 e transcription was enhanced when Bright and Btk were coexpressed.

24 Cells lacking both Bright and Btk were transfected with Bright and/or Btk along with a

25 pe I IgM(low) B cells require Ag-derived and Btk-dependent signals for their development and make up

26 and mast cell function, we generated Itk and Btk double knock-out mice.

27 The Tec family of tyrosine kinases Itk and Btk serve as critical signal amplifiers downstream of an

28 in primary T and B cells relative to Itk and Btk, respectively.

29 Similar studies with Lyn-/- and Btk-/-/Lyn-/- BMMCs indicated that Lyn was a regulator o

30 males, 1 female); UNG in one adult male; and Btk in 3 boys.

31 hat the levels of N-WASP phosphorylation and Btk expression were increased in response to infection,

32 ese data suggested that a third protein, and Btk substrate, must contribute to Bright-enhanced immuno

33 The phosphorylation of Syk and Btk is also down-modulated.

34 Consistent with these results, Lyn, Syk, and Btk are activated in HC IgE-stimulated cells in a slower

35 ata indicate that in mature B cells, Tec and Btk may compete for activation of the Akt signaling path

36 w-derived macrophages, we found that Tec and Btk promote phosphorylation events necessary for immunor

37 cretion and cell-surface exposure by TLR and Btk to target cancer cells for phagocytosis, even if the

38 he levels of phosphorylation of tyrosine and Btk, as well as the levels of F-actin and phosphorylated

39 on are significantly reduced in both xid and Btk inhibitor-treated B cells.

40 tinib) and genetic (in patients with XLA and Btk knockout mice) BTK ablation in primary immune cells

41 of several PH domains, including Akt, ARNO, Btk, DAPP1, Grp1, and C-terminal TAPP1 PH domains by sur

42 and immune cell signaling molecules such as Btk, ROCK and CaMK4.

43 Autoinhibited Btk adopts a compact conformation like that of inactive

44 ly dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-ce

45 f interacts with the Tec family members Bmx, Btk, and Itk but not Tec or Txk.

46 -cell activating factor MoAb and bortezomib, Btk inhibitor) show promise not only in preserving bone

47 eficient only in Btk, mice deficient in both Btk and MyD88 were entirely incapable of generating B. h

48 Furthermore, embryos lacking both Btk and Tec exhibited cutaneous edema associated with bl

49 Furthermore, Bright function required both Btk kinase activity and sequences within the pleckstrin

50 t inhibitory effects toward Itk, followed by Btk and endothelial and epithelial tyrosine kinase.

51 Bright was not appreciably phosphorylated by Btk; however, a third tyrosine-phosphorylated protein co

52 anti-insulin B cell numbers were reduced by Btk deficiency, but not Notch2 haploinsufficiency.

53 onent of the CRT/CD91/C1q system targeted by Btk.

54 e, we used mice with defective btk (CBA/CaHN-Btk(XID)/J [XID mice]) to determine the contribution of

55 tively higher levels of activated CD79alpha, Btk, Plcgamma2 and Erk1/2.

56 esponse to BCR engagement in normal B cells, Btk-deficient B cells exhibited a marked reduction in ph

57 B cell development and function, we crossed Btk-deficient mice (btk(-/-)), which are developmentally

58 Crossing Btk deficiency onto 125Tg mice reveals that, in contrast

59 phorylated PECAM-1 more efficiently than did Btk and required its SH2 domain to perform these functio

60 ed by human and mouse mutations that disrupt Btk function and prevent B-cell maturation at steps that

61 After transplantation of EmuB29-Btk-LV-transduced stem cells, treated mice showed signif

62 The persistent few Btk-deficient anti-insulin B cells remain competent to i

63 udies demonstrated a selective advantage for Btk-transduced B-lineage cells.

64 esident peritoneal macrophages deficient for Btk and Tec secrete less proinflammatory cytokines in re

65 licited peritoneal macrophages deficient for Btk and Tec secrete more proinflammatory cytokines than

66 results elucidate important determinants for Btk inhibitor potency against different signaling pathwa

67 vivo using a fluorescent affinity probe for Btk.

68 AT, SLP-76, and BLNK, which are required for Btk and Itk to couple to PLC-gamma.

69 The requirement for Btk and TxA2 receptor function in GPIb-dependent arteria

70 a cell type-specific TLR inhibitory role for Btk and Tec that is mediated by immunoreceptor activatio

71 emonstrated a hitherto undiscovered role for Btk in apoptotic cell uptake, identifying the molecular

72 ta have revealed a novel regulatory role for Btk in mediating apoptotic cell clearance, with CRT iden

73 These data further support a role for Btk in regulating TLR-induced cytokine production from A

74 These findings unravel a crucial role for Btk in setting the threshold for B-cell activation and c

75 ecent evidence has also supported a role for Btk in TLR signaling.

76 se results demonstrate an essential role for Btk-c-Src signaling in TIM-3-induced DC suppression.

77 previous data indicating important roles for Btk and TFII-I in B lymphocytes.

78 calreticulin (CRT) as a novel substrate for Btk in regulating this response.

79 tor TFII-I was identified as a substrate for Btk several years ago.

80 bone marrow-derived mast cells (BMMCs) from Btk and Lyn knock-out mice, that activation of Btk via L

81 Like T1 cells, mature B cells from Btk- and c-Rel-deficient mice also failed to activate th

82 B-cell progenitors derived from Btk-transduced stem cells exhibited higher levels of Btk

83 the carboxyl terminus of the Btk domain from Btk expressed in 293T as well as DT-40 cells.

84 transcription critically requires functional Btk.

85 In germinal center B cells of human GALT, Btk and Erk are phosphorylated, CD22 is down-regulated,

86 d Syk as requisite tyrosine kinases and Hck, Btk, and protein kinase C theta as contributory kinases

87 l promoter to drive B lineage-specific human Btk expression in Btk/Tec(-/-) mice, a strain that repro

88 In order to determine if Btk is important for Bright function, a transcription ac

89 c(-/-)) as a model for XLA, we determined if Btk gene therapy could correct this disorder.

90 that some XLA-causing mutations might impair Btk phosphorylation.

91 In Btk-/- BMMCs, in which there was a partial reduction in

92 In Btk-deficient B cells, the magnitude of BCR aggregation

93 n, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk

94 ow a single tryptophan mediates allostery in Btk.

95 functional for T cell-independent B cells in Btk(-/-) mice.

96 Defects in Btk cause X-linked immunodeficiency disease in mice and

97 urprisingly, MZ B cells failed to develop in Btk-deficient Notch2(+/-)/NOD mice.

98 ated IL-6 serum levels during endotoxemia in Btk-deficient mice.

99 e B lineage-specific human Btk expression in Btk/Tec(-/-) mice, a strain that reproduces the features

100 from immunodeficient mice with a mutation in Btk failed to produce stable Bright DNA-binding complexe

101 ell receptor signaling, because mutations in Btk are responsible for X-linked agammaglobulinemia (XLA

102 agammaglobulinemia is caused by mutations in Btk resulting in multiple defects in B cell development

103 Mutations in Btk, components of the pre-B cell and B cell receptor (l

104 n steady state PCs and Ab levels observed in Btk(-/-) mice.

105 l responses to phosphorylcholine observed in Btk-deficient mice, and indicate that Bright functions i

106 rmsii IgM response in mice deficient only in Btk, mice deficient in both Btk and MyD88 were entirely

107 onal B cell development and proliferation in Btk(-)/Tec(-) mice but failed to rescue CD5(+) B-1 cell

108 ast to the inhibition of actin remodeling in Btk-deficient B cells, actin polymerization, F-actin acc

109 The impairment of responses in Btk-/- cells correlated with an inability of SCF to augm

110 ell survival and humoral immune responses in Btk-deficient mice.

111 Surprisingly, in Btk-overexpressing mice, naive B cells manifested increa

112 T cell-dependent model Ag was unaffected in Btk(-/-) x MyD88(-/-) mice.

113 sgenic mice overexpressing a kinase inactive Btk mutant.

114 of the Tec kinase family that also includes Btk.

115 red CD19-CreDeltaPB pro-B cell lines induced Btk expression, followed by reduced STAT5 phosphorylatio

116 These results are extended into Btk (Bruton's tyrosine kinase), a Tec family kinase link

117 provides important mechanistic insights into Btk kinase activity and phosphorylation-mediated regulat

118 ication loop downstream of the BCR involving Btk and NF-kappaB that may facilitate BCR-dependent B ce

119 ein we describe a selective and irreversible Btk inhibitor, PCI-32765, that is currently under clinic

120 PCI-32765, a selective, irreversible Btk inhibitor, is a novel, molecularly targeted agent fo

121 Itk(-/-)Btk(-/-) mast cells exhibit hyperactive preformed and LP

122 t, and p38 activation is enhanced in Itk(-/-)Btk(-/-) mast cells, and blockage of phosphatidylinosito

123 c family non-receptor tyrosine kinases (Itk, Btk, Tec, Rlk and Bmx) are characterized by the presence

124 sine kinases (PTKs), that includes Tec, Itk, Btk, Bmx, and Txk, plays an essential role in phospholip

125 a significant elevation in serum IgE in Itk/Btk double knock-out mice.

126 erived mast cells (BMMCs) indicated that Itk/Btk double knock-out BMMCs are defective in degranulatio

127 okine receptor BR3 and the tec family kinase Btk, and proliferated in response to IL-4 plus CD40 stim

128 A role for the Tec kinase Btk in the ERK1/2-independent regulatory pathway was rev

129 r tyrosine kinases Bruton's tyrosine kinase (Btk) and c-Src.

130 hat complexes with Bruton's tyrosine kinase (Btk) and its substrate, transcription initiation factor-

131 ICOSL), and if male, Bruton tyrosine kinase (Btk) and SLAM-associated protein (SAP/SH2D1A).

132 oprecipitates with Bruton's tyrosine kinase (Btk) and that these proteins associate in a DNA-binding

133 th the stimulatory Bruton's tyrosine kinase (Btk) and the inhibitory SHIP-1 are required for efficien

134 ndent kinase IV) and Bruton Tyrosine kinase (Btk) and the phosphatase calcineurin were shown to be ef

135 study, we identify Bruton's tyrosine kinase (Btk) as a linker connecting BCR signaling to actin dynam

136 -)/NOD MZ B cells, Bruton's tyrosine kinase (Btk) deficiency was introduced.

137 Loss of Bruton's tyrosine kinase (Btk) function results in mouse Xid disease characterized

138 nt and activation, Bruton's tyrosine kinase (Btk) functions downstream of multiple TLRs, including TL

139 utation in the mouse Bruton tyrosine kinase (Btk) gene causative for mouse X-linked immunodeficiency

140 Bruton tyrosine kinase (Btk) has a well-defined role in B-cell development, wher

141 preciated role for Bruton's tyrosine kinase (Btk) in actin tail formation in intestinal cells.

142 for the Tec kinase Bruton's tyrosine kinase (Btk) in inflammatory cytokine production.

143 aneous mutation in Bruton's tyrosine kinase (Btk) induces a defect in B-cell development that results

144 signaling kinases, Bruton's tyrosine kinase (Btk) inhibitor ibrutinib and the phosphoinositide 3'-kin

145 Bruton tyrosine kinase (Btk) is a central player in multiple signaling pathways

146 Bruton's tyrosine kinase (Btk) is a critical signaling mediator downstream of the

147 Bruton's tyrosine kinase (Btk) is a Tec family non-receptor tyrosine kinase that p

148 t kinase-inactive, Bruton's tyrosine kinase (Btk) is critical for Bright activity in an in vitro mode

149 Bruton's tyrosine kinase (Btk) is expressed in a variety of hematopoietic cells.

150 The Bruton tyrosine kinase (Btk) is specifically required for BCR signaling as demon

151 Bruton's tyrosine kinase (Btk) mediates TLR signaling in macrophages.

152 Bruton's tyrosine kinase (Btk) plays a central role in signal transduction pathway

153 onstrated that the Bruton's tyrosine kinase (Btk) was required for multiple Mac-1 activation events i

154 Bruton's tyrosine kinase (Btk), a downstream effector of PI3K, signals through B c

155 Bruton's tyrosine kinase (Btk), a Tec-family tyrosine kinase, is essential for B-c

156 ight dimerization, Bruton's tyrosine kinase (Btk), and the Btk substrate, TFII-I, for this activity.

157 m signaling molecule Bruton tyrosine kinase (Btk), but the effects of Btk up-regulation on B-cell fun

158 Mice deficient in Bruton's tyrosine kinase (Btk), despite their known defect in BCR signaling, gener

159 cell-deficient and Bruton's tyrosine kinase (Btk)-deficient mice resulted in fatal disseminated disea

160 in the gene encoding Bruton tyrosine kinase (Btk).

161 tion is dependent on Bruton tyrosine kinase (Btk).

162 c kinase (Csk) and Bruton's tyrosine kinase (Btk).

163 ted kinases, such as Bruton tyrosine kinase (Btk).

164 sine kinase [Syk], Bruton's tyrosine kinase [Btk], phosphatidylinositol 3-kinase [PI 3-kinase], and G

165 investigation of the role of the Tec kinases Btk and Tec kinases in regulating TLR signaling in sever

166 e consistent with a model where Tec kinases (Btk, Tec, Bmx) are required for TLR-dependent signaling

167 observation to two other Tec family kinases, Btk and Tec.

168 the expression of several tyrosine kinases: Btk, Lyn, Syk, and the Blnk adaptor molecule.

169 Insect cell expressed full-length Btk is enzymatically active, but a truncated version of

170 in B-cell receptor signaling, including Lyn, Btk, Hck, Syk, MAPK8, MAPK9, and MAPK10.

171 accounted for by the reduced activity of Lyn/Btk/phospholipase C-gamma2 pathway and constitutive inte

172 terselection of autoreactive B cells, making Btk an attractive therapeutic target in systemic autoimm

173 n the kinase domain of the Tec family member Btk that, when mutated to the closely related leucine, l

174 method to generate Y(551) monophosphorylated Btk kinase domain fragment using the Src family kinase L

175 Neither Btk deficiency nor cyclosporin A prevented FOXO1 protein

176 Thus, we have identified a neutrophil Btk signalosome that is involved in a signaling pathway

177 Reported herein, we have tested nine Btk inhibitors and characterized on a molecular level ho

178 In contrast, neither Bright nor Btk alone led to activation of heavy chain transcription

179 Concurrently, we observe Btk-dependent increases in the levels of phosphatidylino

180 unction(s) missing because of the absence of Btk and that Btk is essential for both bt/VWF-mediated a

181 hosphorylates CRT and that in the absence of Btk, CRT fails to localize with CD91 at the cell surface

182 We find that in the absence of Btk, peripheral B cells show a distinct antibody reperto

183 nt BCR signaling and that, in the absence of Btk, this TLR-mediated stimulation is a required compone

184 The FcepsilonRI-dependent activation of Btk and eicosanoid and ROS generation in bone marrow-der

185 In addition to the expected activation of Btk by membranes containing phosphatidylinositol triphos

186 k and Lyn knock-out mice, that activation of Btk via Lyn plays a key role in promoting synergy.

187 Activation of Btk-c-Src signaling in turn triggered the secretion of s

188 crystallographic and biochemical analyses of Btk, which together reveal molecular details of its auto

189 d provide downstream targets for analysis of Btk function.

190 pathway, whereby the activating capacity of Btk is limited by the presence of Tec kinase.

191 duction in bone marrow-derived mast cells of Btk(-/-) mice.

192 ces within the pleckstrin homology domain of Btk.

193 and the role of the noncatalytic domains of Btk in the activation process.

194 bitor to investigate the biologic effects of Btk inhibition on mature B-cell function and the progres

195 on tyrosine kinase (Btk), but the effects of Btk up-regulation on B-cell function are unknown.

196 Further characterization of both forms of Btk by mass spectrometry showed partial phosphorylation

197 this site may down-regulate the function of Btk by selectively suppressing the B cell calcium signal

198 These negative regulatory functions of Btk in dendritic cells appear to be mediated mainly thro

199 ently, indicating the critical importance of Btk in regulating CRT-driven apoptotic cell uptake.

200 ild-type macrophages mimics the inability of Btk-deficient macrophages to phagocytose apoptotic cells

201 66 is a selective, irreversible inhibitor of Btk.

202 Here we show that knockdown of Btk using RNA interference results in decreased tumor ne

203 XO1 mRNA was impaired in murine knockouts of Btk, BLNK, and PLCgamma2.

204 sing mature B cells expressing low levels of Btk and BLNK.

205 sduced stem cells exhibited higher levels of Btk expression than non-B cells; and marking studies dem

206 the ability to partly compensate for loss of Btk activity in B cell differentiation, although the und

207 Loss of Btk results in defective BAFF-mediated activation of bot

208 Consequently, a large number of Btk inhibitors have been developed.

209 Active site occupancy of Btk was tightly correlated with the blockade of BCR sign

210 In contrast, overexpression of Btk, Itk, or Bmx does not induce NFAT activation.

211 ocked RANKL/M-CSF-induced phosphorylation of Btk and downstream PLC-gamma2 in OCs, resulting in dimin

212 , blocks calcium flux and phosphorylation of Btk and TFII-I and is then discharged from lipid rafts a

213 CR-mediated signaling via phosphorylation of Btk, Syk, Erk1/2, and p38 occurred more rapidly in tumor

214 pon BCR stimulation, even in the presence of Btk.

215 BMMCs indicated that Lyn was a regulator of Btk for these responses.

216 Although the role of Btk in B cells has been extensively studied, the role of

217 important implications regarding the role of Btk in myeloid cell function.

218 Here we show an unexpected role of Btk in osteoclast formation.

219 To date, the role of Btk in regulating TLR7-mediated responses is poorly unde

220 The relative role of Btk-dependent B-cell receptor (BCR) signaling in the ind

221 ese results delineate functional sequelae of Btk activation mediating osteolysis and growth of MM cel

222 by their ability to trigger sequestration of Btk residue Y551.

223 Silencing of Btk or c-Src abrogated the inhibitory effects of TIM-3 o

224 its binding mode in the ATP binding site of Btk.

225 By solving the crystal structures of Btk inhibitors bound to the enzyme, we discovered that t

226 ndicate that Bright functions in a subset of Btk-dependent pathways in vivo, particularly those respo

227 PtdIns(3,4,5)P3, reversible translocation of Btk-PH, Grp1-PH, ARNO-PH, DAPP1-PH, and its L177A mutant

228 matically active, but a truncated version of Btk, composed of only the kinase catalytic domain, is la

229 ese data demonstrate a greater dependence on Btk-mediated BCR signaling for physiologic anti-PS relat

230 on in Tec-deficient B cells was dependent on Btk kinase activity, as ibrutinib treatment restored pS6

231 Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PC

232 and Btk were transfected with Bright and/or Btk along with an immunoglobulin heavy chain reporter co

233 Mice lacking B cells or Btk on a C57BL/6 background succumbed with encephalomyel

234 we show that transgenic mice overexpressing Btk specifically in B cells spontaneously formed germina

235 with an X-linked immunodeficiency phenotype (Btk deficient) are susceptible to virus-induced disease.

236 emonstrated that the in vitro phosphorylated Btk kinase domain has a similar activity as the full-len

237 gnaling through a pathway dependent on PI3K, Btk, IKK2, and JNK.

238 s would have to target both ERK1/2- and PI3K/Btk-dependent pathways.

239 In contrast to ERK1/2, the PI3K/Btk pathway does not regulate cytosolic phospholipase A(

240 strongly support the feasibility of pursuing Btk gene transfer for XLA.

241 to hematopoietic stem cells can reconstitute Btk-dependent B-cell development and function in vivo, a

242 PU.1 and Spi-B regulated Btk directly as shown by chromatin immunoprecipitation a

243 the detailed molecular mechanism regulating Btk activation remains unclear.

244 Follicular type II B cells do not require Btk- or Notch-2-derived signals, make up about a third o

245 effects of PCI-32765, an oral and selective Btk inhibitor, on osteoclastogenesis as well as on multi

246 Similarly, Btk-deficient peritoneal and splenic macrophages secrete

247 edit their BCRs to noninsulin specificities; Btk deficiency preferentially depletes insulin binders f

248 These findings support Btk inhibition as a therapeutic approach for the treatme

249 atively charged glutamic acid (E) suppressed Btk-mediated phospholipase Cgamma2 activation and calciu

250 Secondary transplantation showed sustained Btk expression, viral integration, and partial functiona

251 of multiple protein kinases, including Syk, Btk, PI 3-kinase, and GSK3.

252 luding elevated phosphorylation of Lyn, Syk, Btk, and phospholipase C-gamma2.

253 egulatory events, such as activation of Syk, Btk, JNK, p38, Akt, and NF-kappaB, are substantially red

254 eloid cells, CD95 triggers activation of Syk-Btk/PLCgamma2/Rap1 signaling that ultimately leads to in

255 ential role in IR stress, and that targeting Btk activity may provide a useful approach for preventin

256 ssing because of the absence of Btk and that Btk is essential for both bt/VWF-mediated agglutination-

257 We demonstrate that Btk is activated by TLR4 in primary macrophages and is r

258 The results demonstrate that Btk is downstream of Lyn, Syk, SLP-76, and PI3K; upstrea

259 sium metal dependence study established that Btk requires a second magnesium ion for activity.

260 Our data provide strong evidence that Btk plays a critical role in osteoclast multinucleation

261 We also found that Btk activity is regulated differentially in basophils an

262 ese observations support the hypothesis that Btk mediates BCR-induced proliferation and survival in p

263 In this study, we hypothesized that Btk inhibition would reduce hepatocellular injury in a m

264 rs, Wortmannin and LY294002, indicating that Btk-regulated eicosanoid and ROS production occurs downs

265 In this study we show that Btk also couples the receptor for B cell-activating fact

266 Our results show that Btk directly phosphorylates CRT and that in the absence

267 of cell signaling studies clearly show that Btk is activated by Lyn, a Src family kinase, through ph

268 We also show that Btk-dependent downregulation of Ets1 is important for no

269 We showed that Btk depletion led to a decrease in N-WASP phosphorylatio

270 ssical pathway in response to BAFF such that Btk-deficient B cells exhibit reduced kinase activity of

271 These results suggest that Btk regulates B cell survival by directly regulating the

272 e data demonstrate, for the first time, that Btk is a key regulator of a Kit-mediated amplification p

273 The Btk Y617E mutant could partially restore conventional B

274 ion, Bruton's tyrosine kinase (Btk), and the Btk substrate, TFII-I, for this activity.

275 ts in measureable catalytic activity for the Btk kinase domain in the absence of the regulatory domai

276 also identifies a new set of residues in the Btk kinase domain with high node centrality values indic

277 ote cytokine production was abrogated in the Btk-/- BMMCs.

278 cible T-cell kinase (Itk) is a member of the Btk (Bruton's tyrosine kinase) family of tyrosine kinase

279 Occupancy of the Btk active site by PCI-32765 was monitored in vitro and

280 ite (Y617) near the carboxyl terminus of the Btk domain from Btk expressed in 293T as well as DT-40 c

281 Inhibitors of downstream components of the Btk/BLNK/PLCgamma2 pathway were used to define the mecha

282 These results demonstrate that the Btk family kinase, Tec, cannot provide the function(s) m

283 We show that the Btk/BLNK/PLCgamma2 pathway mediates BCR-induced changes

284 Thus, Btk regulates actin dynamics and Ag transport by activat

285 production, and supplementation of IL-10 to Btk-deficient cultures decreased IL-6 production.

286 suggest that activation by IP6 is unique to Btk.

287 B cells overexpressing wild-type Btk were selectively hyperresponsive to BCR stimulation

288 Thus, unlike Btk and other signalosome components, RasGRP1 deficiency

289 Using Btk- and Tec-deficient mice (BtkTec(-/-)) as a model for

290 ieved to be dependent on signals derived via Btk.

291 c-Rel gene transcription and translation via Btk-dependent mechanisms.

292 essential for normal B cell development when Btk is present, but we also found that Tec-deficient mat

293 y were used to define the mechanism by which Btk signaling inhibits FOXO1 expression.

294 lays both positive and negative roles, while Btk primarily plays a positive role in mast cell Fcepsil

295 finding of in vivo pathology associated with Btk overexpression may have important implications for t

296 protein that preferentially associates with Btk), also known as Sh3bp5 (SH3 domain-binding protein 5

297 This phenotype correlates with Btk-dependent induction of NF-kappaB and AP-1 DNA bindin

298 In addition, experiments with Btk-null B cells revealed off-target effects of ibrutini

299 molecular level how their interactions with Btk define their ability to block different signaling pa

300 nant-negative Bright share similarities with Btk-deficient mice, including decreased serum IgM, poor