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 e conclude that direct activation of Itk and Btk by Nef at the membrane in HIV-infected cells may ove

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

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

29 e demonstrate that Nef recruits both Itk and Btk to the cell membrane and induces constitutive kinase

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

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

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

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

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

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

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

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

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

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

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

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

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

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

44 Autoinhibited Btk adopts a compact conformation like that of inactive

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

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

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

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

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

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

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

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

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

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

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

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

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 ffects comparable to that of the kinase-dead Btk in vivo.

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

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

62 ore, this activation mechanism distinguishes Btk from other Tec family member kinases, Tec and Itk, w

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

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

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

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

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

68 vivo using a fluorescent affinity probe for Btk.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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 that some XLA-causing mutations might impair Btk phosphorylation.

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

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

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

93 ow a single tryptophan mediates allostery in Btk.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

109 k at the cell membrane is a critical step in Btk activation.

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

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

112 sgenic mice overexpressing a kinase inactive Btk mutant.

113 of the Tec kinase family that also includes Btk.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

146 Bruton's tyrosine kinase (Btk) is critical for B cell proliferation and activation

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

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

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

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

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

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

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

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

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

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

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

158 l kinase (Itk) and Bruton's tyrosine kinase (Btk), two Tec-family kinases expressed in HIV-1 target c

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

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

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

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

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

164 (PH-TH) module of Bruton's tyrosine kinase (Btk).

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

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

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

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

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

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

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

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

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

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

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

176 Neither Btk deficiency nor cyclosporin A prevented FOXO1 protein

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

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

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

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

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

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

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 ation and activation, and the development of Btk inhibitors is a vigorously pursued strategy for the

193 suggest that PIP(3)-mediated dimerization of Btk at the cell membrane is a critical step in Btk activ

194 le PIP(3) binding as well as dimerization of Btk on the membrane surface.

195 ces within the pleckstrin homology domain of Btk.

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

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

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

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

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

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

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

203 66 is a selective, irreversible inhibitor of Btk.

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

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

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

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

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

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

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

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 A detailed mechanistic understanding of Btk activation has, however, been lacking.

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

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

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

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

233 were consistent with their known effects on Btk activity.

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

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

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

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

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

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

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

241 In contrast to ERK1/2, the PI3K/Btk pathway does not regulate cytosolic phospholipase 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 response required the activity of SFKs, Syk, Btk, PLCgamma2, and PKC.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

273 Here, inspired by a previous suggestion that Btk activation might depend on dimerization of its lipid

274 This suggests that Btk plays a critical role in the stringency of the B cel

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

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

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

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

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

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

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

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

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

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

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

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

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

288 suggest that activation by IP6 is unique to Btk.

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

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

291 ieved to be dependent on signals derived via Btk.

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

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

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

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

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

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

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

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

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

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