ライフサイエンスコーパス: ITIM

1 ITIM-containing receptors play an essential role in modu

2 (1) establish the importance of the PECAM-1 ITIMs for its inhibitory activity, (2) determine the rel

3 6-11) and membrane-proximal (residues 38-43) ITIMs in mediating the inhibitory signal, we made site-d

4 have extensively characterized CEACAM1 as an ITIM-bearing inhibitory receptor, our findings regarding

5 VZV mutants with both an ITIM mutation and either alanine or arginine substitutio

6 pe II transmembrane glycoprotein carrying an ITIM motif, is believed to be an inhibitory coreceptor o

7 to activate cells, and those that contain an ITIM motif to promote inhibition.

8 yrosine-phosphorylated peptide containing an ITIM (ICAM-1 residues 480-488) showed binding to Shp2 ph

9 In contrast, CD32b contains an ITIM and negatively regulates BCR signaling.

10 Given that TIGIT contains an ITIM motif in its intracellular domain and considering t

11 location and expression of IFN-I genes in an ITIM-dependent manner that can proceed without the invol

12 ted on pDC in response to CpG exposure in an ITIM-independent manner.

13 Human CD94/NKG2A is an ITIM-containing inhibitory receptor expressed by NK cell

14 eceptor (LAIR)-1, also known as CD305, is an ITIM-containing inhibitory receptor, expressed by all le

15 immune inhibitory receptors, CD200R lacks an ITIM in the cytoplasmic domain.

16 l of PD-1 contains two structural motifs, an ITIM and an immunoreceptor tyrosine-based switch motif (

17 Consistent with its possession of an ITIM and ITAM-like sequence, FcRH3 was tyrosine phosphor

18 e proximal signal-transduction pathway of an ITIM-bearing receptor, gp49B, a member of a newly descri

19 In contrast, co-ligation of an ITIM-less form of PECAM-1 had no inhibitory effect.

20 gregation of the Fc gammaRIIB1 transduces an ITIM- and SHIP-independent proapoptotic signal that is d

21 st that gB modulates cell-cell fusion via an ITIM-mediated Y881 phosphorylation-dependent mechanism,

22 inhibitory receptor (KIR) family without an ITIM in their cytoplasmic domain.

23 ts constitutive KIR2DL1 self-association and ITIM phosphorylation.

24 nit of the AP-2 clathrin adaptor complex and ITIM tyrosine residues in the cytoplasmic domain of 3DL1

25 athway consisting of CD226 and T cell Ig and ITIM domain (TIGIT) has been associated with susceptibil

26 T cell Ig and ITIM domain (TIGIT) is a newly identified receptor expre

27 T cell Ig and ITIM domain (TIGIT) is a recently identified coinhibitor

28 T cell Ig and ITIM domain (TIGIT) is an inhibitory receptor expressed

29 that the coinhibitory receptor T cell Ig and ITIM domain (TIGIT) was highly expressed on thymic-deriv

30 els of the inhibitory receptor T-cell Ig and ITIM domain (TIGIT), which results in resistance to immu

31 T cell Ig and ITIM domain receptor (TIGIT), expressed on T, NK, and re

32 eport that T cell immunoreceptor with Ig and ITIM domains (TIGIT) expressed on human memory B cells e

33 CD96), and T-cell immunoreceptor with Ig and ITIM domains (TIGIT) play a crucial role in regulating t

34 (PD-1) and T cell immunoreceptor with Ig and ITIM domains (TIGIT) were committed to a functional line

35 ainst PD1, T-cell immunoreceptor with Ig and ITIM domains (TIGIT), or CD8 before the cancer cells wer

36 AG-3), and T cell immunoreceptor with Ig and ITIM domains (TIGIT).

37 of TIGIT (T cell immunoreceptor with Ig and ITIM domains) and PD-1/PD-L1 (PD-1/L1) may improve respo

38 tor TIGIT (T cell immunoreceptor with Ig and ITIM domains) in both humans and mice.

39 cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and programmed cell death protein 1

40 T cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed

41 hibitory receptor, T cell immunoglobulin and ITIM domain (TIGIT), the co-stimulatory receptor CD226 a

42 -cell immunoreceptor with immunoglobulin and ITIM domain) antibodies have been largely disappointing

43 of the anti-TIGIT (T cell immunoglobulin and ITIM domain) antibody vibostolimab as monotherapy or in

44 -cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) receptors, leading to a predominant

45 -cell immunoreceptor with immunoglobulin and ITIM domains) act at different checkpoints to inhibit au

46 bitory motif (ITIM)-containing proteins, and ITIM proteins CD22 and FCGR2B were found to be direct ta

47 it BCR signaling through consensus ITAMs and ITIMs; however, the extracellular ligands of these recep

48 ceptor tyrosine-based activation motifs) and ITIMs (immunoreceptor tyrosine-based inhibition motifs)

49 cognate immunoreceptor ligand T-cell-Ig-and-ITIM-domain (TIGIT).

50 R2DL4 was sensitive to inhibition by another ITIM-containing receptor.

51 In this study, we report that another ITIM-containing receptor, PECAM1/CD31, regulates Fcgamma

52 study, we report that the B cell-associated ITIM-containing inhibitory receptor, CD72, is expressed

53 containing one typical ITIM and one atypical ITIM sequence.

54 motif (ITAM+) FcgammaR, but kept in check by ITIM motif (ITIM+) FcgammaRIIB-mediated mechanisms.

55 thway of inhibitory signaling is provided by ITIM sequences in the cytoplasmic domains of these other

56 on by ITAM-coupled receptors is regulated by ITIM-containing receptors is, however, poorly understood

57 el for regulation of inhibitory signaling by ITIM-containing receptors that relies on reversible plas

58 (3DL1), due to alterations in the canonical ITIM sequences.

59 e results suggest a critical role of the CD5 ITIM-like motif, which by binding to SHP-1 mediates the

60 In contrast to previously characterized ITIM receptors, TLT1 enhanced, rather than inhibited, Fc

61 osine phosphatase (SHP)-2 to the "classical" ITIM (Y281) but not the "nonclassical" ITIM (Y245).

62 ains and a cytoplasmic tail with a consensus ITIM and a noncanonical ITAM.

63 It has two consensus ITIMs in addition to a putative ITAM sequence in its cyt

64 ivating tyrosine kinases and their consorts, ITIMs mobilize opposing tyrosine and inositol-lipid phos

65 that possess cytoplasmic domains containing ITIM (immunotyrosine inhibition motifs)- and, possibly,

66 e members of a larger superfamily containing ITIM sequences, the inhibitory receptor superfamily (IRS

67 erefore, TLT1 represents a new costimulatory ITIM immunoreceptor and is the second ITIM-bearing recep

68 specific for MHC-I, possesses a cytoplasmic ITIM and is highly expressed on murine pDC.

69 ic binding domain, or within its cytoplasmic ITIM, completely abolished PECAM-1-mediated cytoprotecti

70 ct tyrosine residue in the Ly49Q cytoplasmic ITIM.

71 the "conventional" 2DL4 with the cytoplasmic ITIM (2DL4.1) and two encoding different cytoplasmic tru

72 t prevent NK cell activation via cytoplasmic ITIM.

73 al, but opposite to KIR, the membrane-distal ITIM is of primary importance rather than the membrane-p

74 ity, whereas mutation of the membrane-distal ITIM tyrosine had little effect.

75 g SHP-1 and SHP-2 to its two membrane distal ITIMs.

76 egion indicated that the two membrane-distal ITIMs are essential for this inhibitory potential.

77 PECAM-1 is a dual ITIM-containing receptor that inhibits ITAM-dependent re

78 viding evidence that the ITIMs of other dual ITIM-containing receptors are also sequentially phosphor

79 inhibitory effect was mediated through dual ITIM recruitment of the SH2-containing protein tyrosine

80 enotypes and nonredundant functions for each ITIM-containing receptor in the context of platelet home

81 The role of each ITIM, and of the conserved residues upstream of the tyro

82 tif, whereas the swapped version FcgammaRIIa-ITIM significantly inhibited ADE.

83 CD20 occurs independently of the FcgammaRIIb ITIM, indicating that signaling downstream of FcgammaRII

84 To our knowledge, TLT-1 is the first ITIM-containing receptor carrying a potential Src homolo

85 PECAM-1 was the first ITIM-containing receptor identified in platelets and app

86 results suggest a cell biological basis for ITIM receptor signaling and establish an experimental fr

87 se results demonstrate a functional role for ITIM in the regulation of IL-4-induced proliferation.

88 PIR-B contains four ITIM motifs and is thought to be an inhibitory receptor.

89 cyt lysine cluster, in addition to the gBcyt ITIM and the gHcyt.

90 To determine whether the gBcyt ITIM regulates gB/gH-gL-induced cell-cell fusion in vitr

91 ent on tyrosine phosphorylation of the gp49B ITIMs, and an intact SHP-1 carboxyl SH2 domain.

92 To investigate how ITIM receptor signaling impinges on activating pathways,

93 It is not known how ITIM phosphorylation is initiated and regulated.

94 Taken together, results implicate ITIM interactions with SHIP as a major mechanism of Fc g

95 four tyrosines, two of which are embedded in ITIM-signaling motifs (Y597 and Y667) and are likely inv

96 phorylation of tyrosine residues embedded in ITIMs of the cytoplasmic tail.

97 phosphorylated after ligation, only those in ITIMs influence BCR-mediated signaling.

98 rosine signal transduction motifs, including ITIMs or hemITAMs.

99 central to the initiation of both inhibitory ITIM and stimulatory ITAM signaling, the events that reg

100 argets that contain activating or inhibitory ITIM, ITSM or ITAM motifs; for example, inhibition of th

101 of immunoreceptor tyrosine-based inhibitory (ITIM) motifs in the cytoplasmic domains of the inhibitor

102 an immunoreceptor tyrosine-based inhibitory (ITIM)-like motif, crucial for SHP-1 association.

103 Mechanistically, both intracellular ITIM and ITSM of KIR2DL5 underwent tyrosine phosphorylat

104 ns but differ in the number of intracellular ITIMs (three versus two).

105 Ly49IB6 is ITIM+ and is recognized by 5E6 as well as Ly49I-specific

106 n of cell-surface receptors containing ITAM, ITIM or ITSM tyrosine phosphorylation motifs to the prom

107 ng the cytoplasmic tails containing the ITAM/ITIM motifs, leaving the remainder of the receptor intac

108 imulation by insulin via FcgammaRIIB and its ITIM, SHIP-1 activation, and resulting blunted activatio

109 BCR leads to tyrosine phosphorylation of its ITIM motifs and subsequent Src homology region 2 domain-

110 s the tyrosine phosphatase SHP-1 through its ITIM motif(s).

111 MIS can play an inhibitory role through its ITIM sequences.

112 osphorylation of both CD226 and CD28 via its ITIM-containing intracellular domain (ICD); TIGIT's ICD

113 f a SHP-1-related phosphatase, SHP-2, to KIR ITIMs has not been addressed.

114 ain isoforms of these NK-cell receptors lack ITIM sequences and it has been proposed that these 'non-

115 receptors, whereas other NKG2 proteins lack ITIMs and may potentially transmit positive signals.

116 encodes a different cytoplasmic tail lacking ITIMs.

117 expands the signaling potential of the large ITIM-receptor family and reveals an unsuspected componen

118 These results demonstrate that Ly49A ITIM signaling is critical for NK-cell effector inhibiti

119 The AT(2)-mediated ITIM-independent activation of SHP-1 that is distinct fr

120 unoreceptor tyrosine-based inhibition motif (ITIM) and gH (gHcyt).

121 unoreceptor tyrosine-based inhibition motif (ITIM) in its cytoplasmic tail.

122 unoreceptor tyrosine-based inhibition motif (ITIM) in the gB cytoplasmic domain (gBcyt) and demonstra

123 unoreceptor tyrosine-based inhibition motif (ITIM) sequences in its cytoplasmic domain, which may be

124 unoreceptor tyrosine-based inhibition motif (ITIM) sequences in the KIR cytoplasmic tail [1].

125 unoreceptor tyrosine-based inhibition motif (ITIM) that, when phosphorylated, recruits the SH2-contai

126 unoreceptor tyrosine-based inhibition motif (ITIM), binds to the C-terminal Src homology 2 domain of

127 unoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines I

128 unoreceptor tyrosine-based inhibition motif (ITIM), present in the cytoplasmic domain of Fc gammaRIIB

129 unoreceptor tyrosine-based inhibition motif (ITIM), which undergoes phosphorylation and is recognized

130 unoreceptor tyrosine-based inhibition motif (ITIM)-bearing receptor.

131 unoreceptor tyrosine-based inhibition motif (ITIM)-containing proteins, thereby suppressing phosphati

132 unoreceptor tyrosine-based inhibition motif (ITIM)-containing receptor G6b-B is critical for platelet

133 unoreceptor tyrosine-based inhibition motif (ITIM)-containing receptor, SIRPalpha (a member of the si

134 unoreceptor tyrosine-based inhibition motif (ITIM)-containing receptors have been shown to inhibit si

135 unoreceptor tyrosine-based inhibition motif (ITIM).

136 unoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif

137 unoreceptor tyrosine-based inhibitory motif (ITIM) consensus.

138 unoreceptor tyrosine-based inhibitory motif (ITIM) containing molecule that belongs to the CD300 fami

139 unoreceptor tyrosine-based inhibitory motif (ITIM) encompassing Y223 and an immunoreceptor tyrosine-b

140 unoreceptor tyrosine-based inhibitory motif (ITIM) family of inhibitory receptors, functions prominen

141 ne receptor tyrosine-based inhibitory motif (ITIM) in its cytoplasmic tail.

142 unoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic domain, down-regulates humoral

143 unoreceptor tyrosine-based inhibitory motif (ITIM) known to mediate Fc gamma RIIB1 effects suggest th

144 unoreceptor tyrosine-based inhibitory motif (ITIM) of Ly49A that abolished the inhibitory function of

145 unoreceptor tyrosine-based inhibitory motif (ITIM) phosphorylation.

146 unoreceptor tyrosine-based inhibitory motif (ITIM) that binds and constitutively activates Shp2.

147 unoreceptor tyrosine-based inhibitory motif (ITIM) that, when appropriately engaged, becomes phosphor

148 unoreceptor tyrosine-based inhibitory motif (ITIM), which can recruit SHP-1 and SHP-2.

149 unoreceptor tyrosine-based inhibitory motif (ITIM), which engages Src homology 2 (SH2) domain-contain

150 unoreceptor tyrosine-based inhibitory motif (ITIM), which is restricted to immature DCs (iDCs), monoc

151 unoreceptor tyrosine-based inhibitory motif (ITIM)-containing platelet endothelial cell adhesion mole

152 re immunoreceptor tyrosine inhibitory motif (ITIM)-containing proteins, and ITIM proteins CD22 and FC

153 unoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors inhibit cellular responsivene

154 unoreceptor tyrosine-based inhibitory motif (ITIM)-containing type I transmembrane protein belonging

155 unoreceptor tyrosine-based inhibitory motif (ITIM)-dependent manner.

156 unoreceptor tyrosine-based inhibitory motif (ITIM)-like domain and the tyrosine phosphatase Corkscrew

157 unoreceptor tyrosine-based inhibitory motif (ITIM)-like sequences.

158 unoreceptor tyrosine-based inhibitory motif (ITIM)-like sequences.

159 sphorylated tyrosine-based inhibitory motif (ITIM).

160 unoreceptor tyrosine-based inhibitory motif (ITIM).

161 unoreceptor tyrosine-based inhibitory motif (ITIM).

162 Fc receptor containing an inhibitory motif (ITIM).

163 n a phosphatase recruiting inhibitory motif (ITIM); therefore, we conclude that CD200R represents a n

164 ) FcgammaR, but kept in check by ITIM motif (ITIM+) FcgammaRIIB-mediated mechanisms.

165 unoreceptor tyrosine-based inhibitory motif [ITIM]).

166 noreceptor tyrosine-based inhibition motifs (ITIM) within the cytoplasmic domain of CEACAM1 and the S

167 noreceptor tyrosine-based inhibitory motifs (ITIM) have been implicated in the negative modulation of

168 noreceptor tyrosine-based inhibitory motifs (ITIM) in its cytoplasmic region.

169 noreceptor tyrosine-based inhibitory motifs (ITIM) in their cytoplasmic domains, associate with mouse

170 egion, some of which have inhibitory motifs (ITIM) in their cytoplasmic domains.

171 noreceptor tyrosine-based inhibition motifs (ITIMs) have been described previously in two lineages of

172 noreceptor tyrosine-based inhibition motifs (ITIMs) have been shown to mediate inhibitory properties.

173 noreceptor tyrosine-based inhibition motifs (ITIMs), mediated by the crosslinking of BCR and FcgammaR

174 noreceptor tyrosine-based inhibition motifs (ITIMs).

175 noreceptor tyrosine-based inhibitory motifs (ITIMs) abrogated this restoration.

176 noreceptor tyrosine-based inhibitory motifs (ITIMs) and a binding site for B-catenin.

177 noreceptor tyrosine-based inhibitory motifs (ITIMs) control internalization of antibody bound to CD33

178 noreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic tail, classifying this protein

179 immunoreceptor Tyr-based inhibitory motifs (ITIMs) in its cytoplasmic tail.

180 noreceptor tyrosine-based inhibitory motifs (ITIMs) in monocytes.

181 noreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic domains.

182 ring immunotyrosine-based inhibitory motifs (ITIMs) maintain natural killer (NK) cell tolerance to no

183 noreceptor tyrosine-based inhibitory motifs (ITIMs) of PECAM-1.

184 noreceptor tyrosine-based inhibitory motifs (ITIMs) of the -4L isoform, and associates with Src homol

185 noreceptor tyrosine-based inhibitory motifs (ITIMs) within its cytoplasmic domain, and co-ligation of

186 noreceptor tyrosine-based inhibitory motifs (ITIMs), only the two carboxyl-terminal ITIM tyrosines ar

187 noreceptor tyrosine-based inhibitory motifs (ITIMs).

188 noreceptor tyrosine-based inhibitory motifs (ITIMs).

189 noreceptor tyrosine-based inhibitory motifs (ITIMs).

190 regulatory tyrosine-based inhibitory motifs (ITIMs).

191 noreceptor tyrosine-based inhibitory motifs (ITIMs).

192 noreceptor tyrosine-based inhibitory motifs (ITIMs).

193 ough immunotyrosine-based inhibitory motifs (ITIMs).

194 elates with weak SHP-2 binding to the mutant ITIM of 2DL4 in NK cells and a corresponding nonphosphor

195 hese results show that, like KIR, both NKG2A ITIMs are required for mediating the maximal inhibitory

196 When the ITIM-containing -4L and non-ITIM-containing -4S isoforms are transfected into Jurkat

197 ctivity and production, and the noncanonical ITIM-containing receptor TREM-like transcript-1, which i

198 SHP-1 and SHP-2 through a new, nonclassical ITIM motif, (V/I/L)XpY(M/L/F)XP, which corresponds to th

199 ical" ITIM (Y281) but not the "nonclassical" ITIM (Y245).

200 cells and a corresponding nonphosphorylated ITIM peptide in vitro.

201 Thus, FDF03 is a novel ITIM-bearing receptor selectively expressed by cells of

202 lation is controlled by the accessibility of ITIM to tyrosine phosphatases and that KIR binding to HL

203 of cytoplasmic tails, and/or distribution of ITIM(s) within the cytoplasmic tails.

204 rt inclusion of PECAM-1 within the family of ITIM-containing inhibitors of PTK-dependent signal trans

205 ikely altered the expression and function of ITIM-bearing inhibitory receptors (Siglecs) that bind si

206 ion to interfering with the functionality of ITIM+ FcgammaR, effective anti-idiotypic and antitumoral

207 eared to conform to the established model of ITIM-mediated attenuation of ITAM-driven activation.

208 Consistent with the propensity of ITIM proteins to recruit phosphatases, either MYC or miR

209 lds for IC sensitivity based on the ratio of ITIM to ITAM FcgammaR expression.

210 review, we discuss the diverse repertoire of ITIM-containing receptors in platelets, highlighting int

211 To determine the role of ITIM in the IL-4 signaling pathway, we ablated the ITIM

212 requires tyrosine phosphorylation of KIR on ITIMs in the cytoplasmic domain.

213 2DL4 contains only one ITIM in its cytoplasmic domain and an arginine in its tr

214 the identification of PECAM-1, several other ITIM-containing platelet receptors have been discovered.

215 These results suggest that other ITIM-bearing receptors, many of which have no known func

216 tion involves its recruitment to the phospho-ITIM motif of the inhibitory receptor FcgammaRIIB.

217 and recruits SHP-2 through a phosphorylated ITIM, indicating a potential signaling function in effec

218 can specifically bind to the phosphorylated ITIM of CD33.

219 These inhibitory receptors possess ITIM sequences (for immunoreceptor tyrosine-based inhibi

220 he N-terminal domain of CD37 in a predicted "ITIM-like" motif and mediates SHP1-dependent death, wher

221 esion molecule 1 (PECAM-1) as a prototypical ITIM-bearing receptor, we demonstrate that initiation of

222 ion of the tyrosine in the membrane-proximal ITIM abrogated the ability of KIR to block Ab-dependent

223 inding was mediated by the membrane-proximal ITIM of MIS.

224 importance rather than the membrane-proximal ITIM.

225 alpha-chain (IL-4Ralpha) contains a putative ITIM in the carboxyl terminal.

226 its association with DAP12, and the putative ITIM in the NKp44 cytoplasmic domain does not appear to

227 th pervanadate, but it was unable to recruit ITIM-binding negative effector phosphatases.

228 d by receptors that are not known to recruit ITIMs, we determined the effect of SHIP expression on co

229 ligand for the phosphorylated Fc gamma RIIB1 ITIM, although the SHP-2 decoy exhibits some ability to

230 latory ITIM immunoreceptor and is the second ITIM-bearing receptor to be identified in platelets afte

231 plasma membrane interactions and sequential ITIM phosphorylation.

232 f these findings, we propose that sequential ITIM phosphorylation provides a general mechanism for pr

233 e only other type II KIR, which has a single ITIM) in a human NK-like cell line.

234 city responses; 2) the phosphorylated single ITIM recruits SHP-2 protein tyrosine phosphatase, but no

235 , mutation of the tyrosine within the single ITIM does not completely abolish inhibitory function; an

236 ow in human NK cell lines that 1) the single ITIM of 2DL4 efficiently inhibits natural cytotoxicity r

237 embrane arginine, the function of the single ITIM of 2DL4 remains unknown.

238 andem ITIMs of KIR3DL1 (3DL1) and the single ITIM of 2DL4 were directly compared in functional and bi

239 ases (SFK) excluding Lyn phosphorylate SIRPa ITIMs, leading to the preferential recruitment and activ

240 Furthermore, two FcoR genes can swap ITIMs and hemITAMs by alternative splicing, suggesting t

241 In this study, tandem ITIMs of KIR3DL1 (3DL1) and the single ITIM of 2DL4 were

242 -interacting segment contains the C-terminal ITIM tyrosine and a serine residue that undergo activati

243 the prior phosphorylation of its C-terminal ITIM, providing evidence that the ITIMs of other dual IT

244 family kinases phosphorylate the C-terminal ITIM, thereby enabling phosphorylation of the N-terminal

245 ation of the membrane-interacting C-terminal ITIM.

246 tifs (ITIMs), only the two carboxyl-terminal ITIM tyrosines are required for efficient recruitment of

247 The N-terminal ITIM is excluded from the lipid-interacting segment, and

248 y enabling phosphorylation of the N-terminal ITIM of PECAM-1 by other Src homology 2 domain-containin

249 nally, the phosphorylation of the N-terminal ITIM of Siglec-9 by Csk is enhanced by the prior phospho

250 it was not phosphorylated on its N-terminal ITIM.

251 that this is an oversimplification, and that ITIM-containing receptors are versatile regulators of pl

252 studies using these approaches indicate that ITIM-containing receptors function at least in part by s

253 These results revealed that ITIM phosphorylation is controlled by self-association o

254 The ITIM was not necessary for activation of lysis by KIR2DL

255 n the IL-4 signaling pathway, we ablated the ITIM of IL-4Ralpha by deletion and site-directed mutagen

256 Although the ITIM appears to contain all the structural information r

257 ated, with the N-terminal SH2 domain and the ITIM being most important for the interaction.

258 to bind homophilically are required for the ITIM phosphorylation of CEACAM1 that is a prerequisite f

259 eered that lacked either the tyrosine in the ITIM or an arginine-tyrosine motif in the transmembrane

260 tail distal from residue 237, including the ITIM.

261 rent cytoplasmic truncated forms lacking the ITIM (2DL4.2 and 2DL4(*)).

262 Mutation of the ITIM had little effect on PD-1 signaling or functional a

263 (XmAb5871) stimulated phosphorylation of the ITIM of FcgammaRIIb and suppressed BCR-induced calcium m

264 1/mu2 interaction, either by mutation of the ITIM tyrosines in 3DL1 or mutation of mu2, significantly

265 n sequential tyrosine phosphorylation of the ITIM, recruitment and phosphorylation of p145SHIP, and s

266 Like engagement of the ITIM-bearing receptor LAIR-1/p40, cross-linking of FDF03

267 R2B-187I, independent of the presence of the ITIM.

268 ls revealed that these processes require the ITIM (immunoreceptor tyrosine-based inhibition motif) of

269 ar activation potential, indicating that the ITIM does not influence 2DL4.1 activating function.

270 ed with wild-type cells, indicating that the ITIM mutants phenocopied the Ser508 mutants.

271 It has long been known that the ITIM-bearing IgG Fc receptor (FcgammaRIIb, RIIb) is expr

272 Using peptides corresponding to the ITIM of hIL-4Ralpha, we demonstrate that tyrosine-phosph

273 trometry confirmed that Y881, central to the ITIM, is phosphorylated.

274 When the ITIM-containing -4L and non-ITIM-containing -4S isoforms

275 FcgammaRs with the ITIM domain have been shown to regulate the inflammatory

276 The association of SHIP with the ITIM phosphopeptide was activation independent, while co

277 Disruption of the ITIMs by introduction of point mutations not only preven

278 bly reflects the opposite orientation of the ITIMs in type II vs type I proteins.

279 C-terminal ITIM, providing evidence that the ITIMs of other dual ITIM-containing receptors are also s

280 mplex with the inhibition dependent upon the ITIMs of CEACAM1 and Src homology 2 domain-containing ph

281 strate that the tyrosine residues within the ITIMs are phosphorylated and serve for the association a

282 face levels of inhibitory KIRs through their ITIM domains.

283 Phosphopeptides corresponding to these ITIMs could bind the Src homology 2 (SH2) domain-contain

284 Furthermore, this ITIM-mediated mechanism may similarly regulate the surfa

285 The role of this ITIM on the activating function of KIR2DL4, and whether

286 in an NK-like cell line, we found that this ITIM-like motif from NKp44 lacks inhibitory capacity in

287 PAMPs, and competes with SHP-1/2 binding to ITIMs of cytokine receptors, thereby inhibiting signalin

288 recruiting protein tyrosine phosphatases to ITIMs.

289 omain, and a cytoplasmic tail containing two ITIM-signaling motifs.

290 d on activated human T cells and possess two ITIM motifs in the CT.

291 28) is distinct and independent from the two ITIM tyrosines required for efficient SHP-1 recruitment

292 ler cell Ig-like receptors (KIR) contain two ITIMs.

293 rs because its cytoplasmic tail contains two ITIMs at Y245 and Y281.

294 s of KIR2DL5, KIR3DL1 (a type I KIR with two ITIMs), and KIR2DL4 (the only other type II KIR, which h

295 tracytoplasmic domain containing one typical ITIM and one atypical ITIM sequence.

296 osphorylation null mutations in the tyrosine ITIMs known to be phosphorylated by the tyrosine kinase

297 Whether ITIM phosphorylation is similarly regulated and the mech

298 rnalization, raising the question of whether ITIM phosphorylation plays any role in this process.

299 lation of cytosolic tyrosine residues within ITIMs results in recruitment of a protein tyrosine phosp

300 ndent on the SHP-2 recruiting classical Y281 ITIM.