ライフサイエンスコーパス: SHIP1

1 2 domain-containing inositol phosphatase 1 (SHIP1).

2 y-2 (SH2)-containing inositol 5 phosphase-1 (SHIP1).

3 sent in cells expressing the S440A mutant of SHIP1.

4 l DT40 B lymphocytes expressing native mouse SHIP1.

5 o a stoichiometry of 0.6 mol of PO(4)/mol of SHIP1.

6 id also increased the phos pho ryl a tion of SHIP1.

7 r increased the phos pho ryl a tion state of SHIP1.

8 through downregulation of the Akt inhibitor, Ship1.

9 RIIIa-induced NK cell cytokine production by SHIP1.

10 he N-terminal SH2 domain region contained in SHIP1.

11 omology 2-containing inositol 5-phosphatase, SHIP1.

12 ne BCR/ABL drastically reduces expression of SHIP1.

13 OK1 binds directly through its PTB domain to SHIP1.

14 PSTPIP2 binds the inhibitory enzymes Csk and SHIP1.

15 ncy and increase the catalytic efficiency of SHIP1.

16 actions, and the activation of autoinhibited SHIP1.

17 pe can be rescued by extrinsic expression of SHIP1.

18 e to determine the NK cell-intrinsic role of SHIP1.

19 cells, at least in part via down-regulating SHIP1.

20 s direct effects on the inositol phosphatase SHIP1.

21 metry analyses, we found that CD2AP bound to SHIP1.

22 ther antagomir-155 or elevated expression of SHIP1.

23 ern blot analysis, we observed that blocking Ship1/2 abrogated EMC cell survival by exerting dual eff

24 Treatment of EMC cell lines with Ship1/2 small molecule inhibitors resulted in the induct

25 he identification of a chemical inhibitor of SHIP1, 3 alpha-aminocholestane (3AC).

26 NF mRNA half-life and limiting expression of SHIP1, a negative regulator of the PI3K/Akt pathway.

27 ion induced an increase in the expression of SHIP1, a phosphatase that negatively regulates the PI3K

28 ere, we show that recruitment of phosphatase SHIP1, a process governed by a single amino acid residue

29 evels (including inhibitory molecules SOCS1, SHIP1, A20 and IkappaBalpha), exerting an overall inhibi

30 Mutation of Ser(440) to Ala in full-length SHIP1 abrogated the ability of PKA to increase the activ

31 Indeed, SHIP1 activation mediated the increased expression of Mc

32 HIP1 recruitment, gB-activated EGFR mediated SHIP1 activation, underscoring the importance of the int

33 AQX-1125 is a first-in-class, oral SHIP1 activator with a novel anti-inflammatory mode of a

34 AQX-1125, a novel oral SHIP1 activator, significantly reduces the late response

35 Increased SHIP1 activity is associated with reductions in sMLA-ind

36 in kinase (PKA), resulting in an increase in SHIP1 activity.

37 we identified the serine residue regulating SHIP1 activity.

38 tation to show that Msp moderately decreases SHIP1 activity.

39 The SHIP1/Akt pathway therefore suppresses bone loss in path

40 n 3 [DDX3X]) and feed-forward (i.e., miR-155/SHIP1/AKT/miR-126) regulatory loops that eventually conv

41 Knockdown of CD2AP or SHIP1 also enhanced the ubiquitination and degradation o

42 t stem cell (iPSC)-derived microglia lacking SHIP1 also showed increased engulfment of synaptic struc

43 ished expression of the inositol phosphatase SHIP1 and increased activation of ERK and AKT kinases.

44 Further, we found that SHIP1 and IRAK-M, direct targets of miR-155 that are kno

45 ion of endotoxin tolerance via modulation of SHIP1 and IRAK-M.

46 unveils a molecular link between miR-155 and SHIP1 and provides evidence that repression of SHIP1 is

47 hosphorylation of the 5-inositol phosphatase SHIP1 and requires SHIP1 expression.

48 or-mediated signaling, our finding that both SHIP1 and SHIP2 are constitutively tyrosine phosphorylat

49 First, SHIP1 and SHIP2 are potent inhibitors of Tec activity.

50 y, we show that the inositol 5' phosphatases SHIP1 and SHIP2 interact preferentially with Tec, compar

51 These observations suggest (1) that SHIP1 and SHIP2 may have a different hierarchy of bindin

52 matic difference raises the possibility that SHIP1 and SHIP2 may serve different functions.

53 e two proteins, we demonstrate that, whereas SHIP1 and SHIP2 selectively hydrolyze PtdIns(3,4,5)P3 in

54 Despite their high sequence identity (51%), SHIP1 and SHIP2 share little overlap in their in vivo fu

55 f phosphatidylinositol-3,4,5-triphosphate by SHIP1 and SHIP2-recruits lamellipodin, which in turn eng

56 opied the effects of cold exposure, reducing Ship1 and Socs1 and altering TNF and IL-10 production.

57 2 degrees C and miR-155 antagomirs increased Ship1 and Socs1 and reversed the alterations in cytokine

58 Indeed, Ship1 and Socs1 were suppressed at 32 degrees C and miR-

59 iated with increased miR-155, suppression of Ship1 and Socs1, and alterations in TNF and IL-10.

60 tor (TLR) signaling by negatively regulating Ship1 and Socs1.

61 Lymphoid cells with defects in SHIP1 and/or ptase and tensin homolog deleted on chromos

62 domain-containing inositol 5-phosphatases 1 (SHIP1) and 2 (SHIP2) are structurally similar proteins t

63 tly decreased IFN-gamma production from both SHIP1-/- and WT NK cells under these conditions.

64 tive signals driven by the lipid phosphatase Ship1; and slower degradation of Ship1 co-factors.

65 The lipid phosphatases PTEN and SHIP1 are critical in regulating the level of PtdIns(3,4

66 ments suggest that Tyr(917) and Tyr(1020) in SHIP1 are likely to mediate interactions with DOK1.

67 the endogenous levels of the miR-155 target, SHIP1, are consistently elevated in EBV- and HTLV1-trans

68 ation of 17 serine and threonine residues on SHIP1 as being phosphorylated by PKA in vitro, studies w

69 domain-containing inositol 5-phosphatase 1 (SHIP1) as a direct target of miR-155, and, using gain an

70 L-transformed Ba/F3 cell line and identified SHIP1-associated proteins.

71 We have found that SHIP1 associates and colocalizes with the HIP1/PDGFbetaR

72 SHIP1 autoinhibition can be relieved through interaction

73 phosphatase activity, it is not required for SHIP1 autoinhibition.

74 cells indicate that both Ptyr SHIP2 and Ptyr SHIP1 bind to the PTB domain of SHC but not to its SH2 d

75 Overexpression of wild-type (WT) SHIP1, but not a catalytic-deficient mutant, via retrovi

76 PKA increased the 5' phosphatase activity of SHIP1 by 2-3-fold.

77 We also report that phosphorylation of SHIP1 by HIP1/PDGFbetaR does not change its 5-phosphatas

78 Repression of endogenous SHIP1 by miR-155 occurred following sustained over-expre

79 These results suggest that activation of SHIP1 by PKA via phosphorylation on Ser(440) is an impor

80 Knockdown of endogenous SHIP1 by shSHIP1 RNA decreases native and inducible IRAK

81 ld type SHIP1, expression of tyrosine mutant SHIP1 by transient transfection did not alter migration.

82 This suggests that SHIP1 calibrates the threshold of iNKT cell reactivity.

83 SHIP1 can be phosphorylated by the cyclic AMP-dependent

84 complex induced the recruitment of the CD2AP/SHIP1/Cbl complex to the plasma membrane of pDCs, where

85 phosphatase Ship1; and slower degradation of Ship1 co-factors.

86 er that, upon BDCA2 cross-linking, the CD2AP/SHIP1 complex associated with Cbl and inhibited its E3 u

87 domain-containing inositol 5-phosphatase 1 (SHIP1) controls the dephosphorylation of PI(3,4,5)P(3) t

88 that the effect of Sp-cAMPS in DT40 cells is SHIP1-de pend ent.

89 3 levels in B cells by CD19 cross-linking or SHIP1 deficiency eliminated the negative regulatory effe

90 in certain cell types that are the result of SHIP1 deficiency in cells in separate and distinct linea

91 SHIP1-deficient microglia showed altered transcriptional

92 2 domain-containing inositol-5-phosphatase [Ship1])-deficient mice experience spontaneous airway inf

93 Germline SHIP1 deletion has been shown to affect T cells as well

94 We evaluated the consequences of SHIP1 deletion on iNKT cells using germline-deficient mi

95 We hypothesized that SHIP1 deletion would have major effects on iNKT cell dev

96 Unlike germline panhematopoietic Ship1 deletion, deletion of Ship1 selectively in either

97 or dendritic cells (DCs), and the resulting Ship1(DeltaB cell), Ship1(DeltaT cell), Ship1(DeltaDC),

98 ting Ship1(DeltaB cell), Ship1(DeltaT cell), Ship1(DeltaDC), or Ship1(F/F) (wild-type) control mice w

99 (DCs), and the resulting Ship1(DeltaB cell), Ship1(DeltaT cell), Ship1(DeltaDC), or Ship1(F/F) (wild-

100 e likely to be involved in the regulation of SHIP1 dependent migration.

101 nt of CD32b, a result also consistent with a SHIP1-dependent mechanism of inhibition.

102 domain-containing inositol 5'-phosphatase 1 (SHIP1) dephosphorylates phosphatidylinositol 3,4,5-trisp

103 d that mice conditionally lacking microglial SHIP1 displayed increased complement and synapse loss in

104 h is critical to aberrant Akt activation, as SHIP1 diverts PI3K signaling toward a noncanonical pathw

105 In contrast, SHIP1 does not associate with H/P(KI), the kinase-dead f

106 Loss of SHIP1 elevates Akt activation following cell adhesion du

107 Although dimerization of SHIP1 enhances membrane localization and the apparent ph

108 presence of elevated GC levels up-regulated SHIP1 expression and increased their capacity to produce

109 IL-8 in CF lung epithelial cells by lowering SHIP1 expression and thereby activating the PI3K/Akt sig

110 Moreover, we show SHIP1 expression by NK cells is required for in vivo-mis

111 Alterations in SHIP1 expression have been shown to perturb myeloid cell

112 pothesized that lineage-specific deletion of Ship1 expression in cells known to be crucial for adapti

113 rides IL-12 and IL-18-mediated regulation of SHIP1 expression in NK cells.

114 expression, indicating that GCs can regulate SHIP1 expression in vivo.

115 Small interfering RNA-mediated knockdown of SHIP1 expression increased PI3K-dependent Akt activation

116 ion, suggesting GC-mediated up-regulation of SHIP1 expression is responsible for the augmentation in

117 dicating that TGF-beta1 regulates IRAK-M and SHIP1 expression through a SMAD4-dependent pathway.

118 the LPS responsiveness of Mphi by augmenting SHIP1 expression through a TGF-beta-dependent mechanism.

119 GC-conditioning of BMMphi enhanced SHIP1 expression via up-regulation of bioactive TGF-beta

120 Ship1 expression was deleted in B cells, T cells, or den

121 an enhanced LPS responsiveness and increased SHIP1 expression, indicating that GCs can regulate SHIP1

122 he 5-inositol phosphatase SHIP1 and requires SHIP1 expression.

123 In contrast to wild type SHIP1, expression of tyrosine mutant SHIP1 by transient

124 ell), Ship1(DeltaT cell), Ship1(DeltaDC), or Ship1(F/F) (wild-type) control mice were evaluated in a

125 lternative STAT3-independent pathway through SHIP1 for IL-10 to regulate TNFalpha translation during

126 We prepared pure recombinant SHIP1 from HEK-293 cells and found it can be rapidly pho

127 possible PDGFbetaR-mediated sequestration of SHIP1 from its substrates (PtdIns(3,4,5)P(3) and Ins(1,3

128 c homology 2-containing inositol phosphatase SHIP1 functions in hemopoietic cells to limit activation

129 trolled by a promoter within intron 5 of the ship1 gene.

130 activity in ES cells of an intron 5/intron 6 ship1 genomic segment and its tissue specificity within

131 Although SHIP1 has been shown to regulate neutrophil chemotaxis,

132 partial MyD88 activity, with MyD88-dependent SHIP1 helping to reduce proinflammatory signaling in DCs

133 ely hydrolyze PtdIns(3,4,5)P3 in vitro, only SHIP1 hydrolyzes soluble Ins(1,3,4,5)P4.

134 IP1 in hematopoietic cells, we overexpressed SHIP1 in a murine BCR/ABL-transformed Ba/F3 cell line an

135 ates the anti-inflammatory lipid phosphatase SHIP1 in an MyD88-dependent manner.

136 The major effect of re-expressing SHIP1 in BCR/ABL-transformed cells is reduction of hyper

137 Indeed, overexpression of SHIP1 in CD56bright NK cells followed by monokine activa

138 -155 influenced the level of the phosphatase SHIP1 in DCs and that the lack of SHIP1 in DCs was suffi

139 hosphatase SHIP1 in DCs and that the lack of SHIP1 in DCs was sufficient to break T cell tolerance in

140 eage did not affect HDM-induced AAI, loss of Ship1 in either of the T-cell or DC lineages protected m

141 e the potential signaling pathways involving SHIP1 in hematopoietic cells, we overexpressed SHIP1 in

142 e ability of PKA to increase the activity of SHIP1 in mammalian cells.

143 ytokine production because overexpression of SHIP1 in primary bone marrow Mphi (BMMphi) leads to a si

144 ous lung inflammation, selective deletion of Ship1 in T cells or DCs impairs the formation of an adap

145 Strikingly, although loss of Ship1 in the B-cell lineage did not affect HDM-induced A

146 In mice, specific knockdown of SHIP1 in the hematopoietic system following retroviral d

147 are the first to show a physiologic role for SHIP1 in the regulation of NK cell cytokine production a

148 Phosphorylation of SHIP1 in vitro or in cells by PKA increased the 5' phosp

149 se SH2-containing-inositol-5'-phosphatase-1 (SHIP1) induces acute cell death in CLL cells.

150 On one hand, specific Ship1 inhibition enhanced calcium signaling and thereby

151 suppression of IL-1beta processing and that SHIP1 inhibition results in the enhancement of this proc

152 tored neutrophil migratory accuracy, whereas SHIP1 inhibition worsened migratory flaws.

153 ROS-induced cell death and suggest transient SHIP1-inhibition as an unexpectedly promising concept fo

154 Thus, SHIP1 inhibitors represent a novel class of small molecu

155 Third, SHIP1 inhibits Tec membrane localization.

156 SHIP1 is a 5' inositol phosphatase that dephosphorylates

157 SHIP1 is a 5'-inositol phosphatase known to negatively r

158 IP1 and provides evidence that repression of SHIP1 is an important component of miR-155 biology.

159 SHIP1 is an SH2 domain containing inositol-5-phosphatase

160 The expression of SHIP1 is augmented in 11betaHSD1(-/-) Mphi and contribut

161 Molecular dissection reveals that SHIP1 is autoinhibited with the N-terminal Src homology

162 e structural and functional relationships of SHIP1 is critical for developing ways to modulate SHIP1

163 ere, we show that constitutive expression of SHIP1 is distinctly lower in CD56bright NK cells compare

164 SHIP1 is essential for normal bone homeostasis, as mice

165 These findings suggest that SHIP1 is essential for proper microglia-mediated synapse

166 However, SHIP1 is expressed in all hematopoietic lineages, and co

167 alization of the central catalytic domain of SHIP1 is insensitive to dynamic changes in PI(3,4,5)P(3)

168 The interaction with SHIP1 is of particular importance because it binds to th

169 SHIP1 is recruited to a large number of inhibitory recep

170 In contrast, SHIP1 is required cell autonomously for optimal iNKT cel

171 ositol polyphosphate-5-phosphatase D (INPP5D/SHIP1) is a myeloid-expressed gene genetically-associate

172 SH2-containing inositol-5'-phosphatase 1 (SHIP1) is an endogenous inhibitor of the phosphoinositid

173 ning inositol polyphosphate 5-phosphatase 1 (SHIP1) is an immune cell-specific enzyme that regulates

174 logy 2-containing inositol 5'-phosphatase 1 (SHIP1) is known to exert inhibitory effects on Fc recept

175 ning inositol polyphosphate 5-phosphatase 1 (SHIP1), is associated with the risk of Alzheimer's disea

176 genesis by BMMs derived from STAT6-, but not SHIP1-, knockout mice.

177 at increased AKT activity upon inhibition of SHIP1 leads to increased mitochondrial respiration and c

178 Although panhematopoietic deletion of Ship1 leads to spontaneous lung inflammation, selective

179 , transient expression of IRF4 decreases the SHIP1 level in EBV-negative B cells.

180 Genetic studies revealed that SHIP1 limits blood cell production and immune regulatory

181 ively targeting Tec to the membrane relieves SHIP1-mediated inhibition.

182 Very transient SHIP1 membrane interactions were detected only when memb

183 d the CBL1 motif of the C2 domain that limit SHIP1 membrane localization and activity.

184 is critical for developing ways to modulate SHIP1 membrane localization and lipid phosphatase activi

185 Robust SHIP1 membrane localization and relief of autoinhibition

186 nd protein interactions serve in controlling SHIP1 membrane recruitment and activity remains unclear.

187 ular bone erosions are markedly increased in SHIP1(-/-) mice with inflammatory arthritis, a condition

188 id-associated lung consolidation observed in SHIP1(-/-) mice.

189 In addition, NK cells from SHIP1-/- mice produced 10-fold greater amounts of IFN-ga

190 Finally, NK cells in SHIP1-/- mice produced more IFN-gamma in response to mon

191 We postulated that molecular targeting of SHIP1 might enhance blood cell production and increase i

192 not seen when NK cells were infected with a SHIP1 mutant containing an inactive catalytic domain.

193 in vitro, studies with truncation mutants of SHIP1 narrowed the phosphorylation site to the catalytic

194 Collectively, these results demonstrate that SHIP1 negatively regulates monokine-induced NK cell IFN-

195 SHIP1((-)/(-)) neutrophils lose their polarity upon cell

196 of PI3-K) was significantly enhanced within SHIP1-/- NK cells compared with WT NK cells following co

197 In this study, we show that BMMs from SHIP1 null mice respond to M-CSF, but not receptor activ

198 eam of B cell antigen receptor engagement in SHIP1-null DT40 B lymphocytes expressing native mouse SH

199 Single-molecule measurements of purified SHIP1 on supported lipid bilayers and in neutrophil-like

200 lized membrane recruitment and activation of SHIP1 on supported lipid bilayers and the cellular plasm

201 However, the role of SHIP1 on T cell function has been controversial, and its

202 However, overexpressing SHIP1 or inhibition of PI3K in CF cells suppressed IL-8

203 ics of SHIP1 phosphorylation as a measure of SHIP1 participation in the reaction.

204 induced mast cell activation via FcgammaRIIB/SHIP1 pathway, resulting in a decrease of brain inflamma

205 SHIP1 phosphatase release was assessed using chemical in

206 The EC50s for phospho-Src, phospho-SHIP1, phospho-Syk, or phospho-Cbl did not change while

207 examined the changes and characteristics of SHIP1 phosphorylation as a measure of SHIP1 participatio

208 First, the kinetics of SHIP1 phosphorylation were similar to reaction kinetics

209 by engagement of CD32b (lyn, syk, SHP-1, or SHIP1 phosphorylation) was more consistent with a mode o

210 of IVIG were mediated, at least partly, via SHIP1/PIP3 pathway.

211 deletion mouse model of SHIP1, we show that SHIP1 plays a profound NK lineage-intrinsic role in NK c

212 SHIP1 plays an important role in processes, such as dire

213 and a central catalytic region, SHIP2 (like SHIP1) possesses both potential PTB(NPXY) and SH3 domain

214 From our observations, we conclude that SHIP1 prevents formation of top-down PtdIns(3,4,5)P(3) p

215 suggests that SHIP2, like that reported for SHIP1 previously, is linked to downstream signaling even

216 P protein is a shorter isoform of the longer SHIP1 protein and lacks the N-terminal SH2 domain region

217 -beta1 treatment does not increase IRAK-M or SHIP1 protein expression in shSMAD4 THP-1 cells, whereas

218 ose LPS exposure does not increase IRAK-M or SHIP1 protein expression in small hairpin (sh)SMAD4 THP-

219 domain-containing inositol 5-phosphatase 1 (SHIP1)/protein kinase B (Akt) pathway.

220 defect in neutrophils led to the belief that SHIP1 rather than PTEN acts as a predominant phospholipi

221 e consistent with a mode of action involving SHIP1 rather than SHP-1.

222 Although integrin beta1 was required for SHIP1 recruitment, gB-activated EGFR mediated SHIP1 acti

223 Knockdown of CD2AP or SHIP1 reduced the BDCA2/FcepsilonR1gamma-mediated ITAM s

224 In the brain, SHIP1 regulates microglial cell behaviors, which have be

225 In this study, we show that SHIP1 regulates PtdIns(3,4,5)P(3) production in response

226 2 domain-containing inositol 5' phosphatase, SHIP1, regulates hematopoietic cell function by opposing

227 These results outline a novel mechanism of SHIP1 regulation.

228 D5 to positive (PI3K) and negative (UBASH3A, SHIP1) regulators of TCR signaling.

229 sphorylate the purified, catalytic domain of SHIP1 (residues 401-866).

230 elivery of a miR-155-formatted siRNA against SHIP1 resulted in a myeloproliferative disorder, with st

231 ions that loss of PTEN had minor and loss of SHIP1 resulted in a severe chemotaxis defect in neutroph

232 , our results provide new insight concerning SHIP1's structural organization, membrane binding dynami

233 ively bind to the SH3 domain of ABL, whereas SHIP1 selectively binds to the SH3 domain of Src.

234 panhematopoietic Ship1 deletion, deletion of Ship1 selectively in either the B-cell, T-cell, or DC li

235 tically different binding kinetics, with the SHIP1 SH2 domain having fast association and dissociatio

236 of its specificity profile with that of the SHIP1 SH2 domain showed that the two SH2 domains have si

237 at the pY + 1 position by the SHIP2 but not SHIP1 SH2 domain.

238 slation suppression requires the presence of SHIP1 (SH2 domain-containing inositol 5'-phosphatase 1)

239 Furthermore, in contrast to SHIP1, SHIP2 did not bind to either the N-terminal or C-

240 On the other hand, concomitant Ship1/Ship2 inhibition or specific Ship2 inhibition redu

241 Inhibition of SHIP1/SHIP2 reduced cellular survival and S6 phosphoryla

242 etion of Ship2, but not of its close homolog Ship1, significantly reduced CLL formation in IgH.TEmu m

243 < 0.05), which was associated with increased Ship1, Socs1, and IL-10.

244 (32)P-labeled HEK-293 cells transfected with SHIP1, stimulation with Sp-adenosine 3',5'-cyclic monoph

245 discovered that the N-terminal SH2 domain of SHIP1 suppresses lipid phosphatase activity.

246 ntrast to the limited cellular expression of SHIP1, the related isoform SHIP2, is widely expressed in

247 lates SH2-containing inositol phosphatase 1 (SHIP1), thereby increasing phosphor-protein kinase B (AK

248 ls of miR-155 specifically reduced levels of SHIP1, thereby promoting PI3K/Akt activation.

249 tion approaches, show that miR-155 represses SHIP1 through direct 3'UTR interactions that have been h

250 ata suggest that proteins that interact with SHIP1 through Tyr(917) and Tyr(1020), such as DOK1 and S

251 oupled receptors that raise cyclic AMP cause SHIP1 to be phosphorylated and stimulate its inositol ph

252 nR1gamma signaling by forming a complex with SHIP1 to inhibit the E3 ubiquitin ligase Cbl.

253 redirection of the PIP3 substrate away from SHIP1 to PTEN.

254 ly, we also find that chemical inhibition of SHIP1 triggers apoptosis of blood cancer cells.

255 ation by IL-4, we used mice lacking STAT6 or SHIP1, two adapter proteins that bind the IL-4 receptor.

256 Furthermore, activating SHIP1 using a small-molecule agonist mimics the inhibito

257 Furthermore, SHIP1 was also repressed by physiologically regulated mi

258 ve defects in adulthood only when microglial SHIP1 was depleted early postnatally but not at later st

259 Here, we showed that SHIP1 was enriched in early stages of healthy brain deve

260 SHIP1 was found to form a novel signaling complex with B

261 We tested to see whether the activity of SHIP1 was regulated via phos pho ryl a tion with PKA.

262 domain-containing inositol 5-phosphatase 1 (SHIP1) was recruited to the gH/integrin beta1 complex, w

263 -molecule inhibitor of INPP5D (also known as SHIP1), we demonstrated that pharmacological hyperactiva

264 an NK cell-specific deletion mouse model of SHIP1, we show that SHIP1 plays a profound NK lineage-in

265 Mice with germline deficiency in SHIP1 were shown to have a defective NK cell compartment

266 ning inositol 5' phosphatase), in particular SHIP1, which activation leads to hydrolyzation of PIP3 (

267 Direct interaction of SHIP1 with CRKL was mediated through the CRKL-SH2 domain

268 SHIP1-YFP and p85-YFP were recruited to forming phagosom

269 SHIP1-YFP sequestered to the leading edge and dissociate