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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
5 pe II transmembrane glycoprotein carrying an ITIM motif, is believed to be an inhibitory coreceptor o
7 yrosine-phosphorylated peptide containing an ITIM (ICAM-1 residues 480-488) showed binding to Shp2 ph
10 location and expression of IFN-I genes in an ITIM-dependent manner that can proceed without the invol
13 eceptor (LAIR)-1, also known as CD305, is an ITIM-containing inhibitory receptor, expressed by all le
15 l of PD-1 contains two structural motifs, an ITIM and an immunoreceptor tyrosine-based switch motif (
17 e proximal signal-transduction pathway of an ITIM-bearing receptor, gp49B, a member of a newly descri
19 gregation of the Fc gammaRIIB1 transduces an ITIM- and SHIP-independent proapoptotic signal that is d
20 st that gB modulates cell-cell fusion via an ITIM-mediated Y881 phosphorylation-dependent mechanism,
23 nit of the AP-2 clathrin adaptor complex and ITIM tyrosine residues in the cytoplasmic domain of 3DL1
24 athway consisting of CD226 and T cell Ig and ITIM domain (TIGIT) has been associated with susceptibil
28 that the coinhibitory receptor T cell Ig and ITIM domain (TIGIT) was highly expressed on thymic-deriv
29 els of the inhibitory receptor T-cell Ig and ITIM domain (TIGIT), which results in resistance to immu
32 hibitory receptor, T cell immunoglobulin and ITIM domain (TIGIT), the co-stimulatory receptor CD226 a
33 -cell immunoreceptor with immunoglobulin and ITIM domains) act at different checkpoints to inhibit au
34 bitory motif (ITIM)-containing proteins, and ITIM proteins CD22 and FCGR2B were found to be direct ta
35 it BCR signaling through consensus ITAMs and ITIMs; however, the extracellular ligands of these recep
36 ceptor tyrosine-based activation motifs) and ITIMs (immunoreceptor tyrosine-based inhibition motifs)
39 study, we report that the B cell-associated ITIM-containing inhibitory receptor, CD72, is expressed
42 thway of inhibitory signaling is provided by ITIM sequences in the cytoplasmic domains of these other
43 on by ITAM-coupled receptors is regulated by ITIM-containing receptors is, however, poorly understood
44 el for regulation of inhibitory signaling by ITIM-containing receptors that relies on reversible plas
46 e results suggest a critical role of the CD5 ITIM-like motif, which by binding to SHP-1 mediates the
51 ivating tyrosine kinases and their consorts, ITIMs mobilize opposing tyrosine and inositol-lipid phos
52 that possess cytoplasmic domains containing ITIM (immunotyrosine inhibition motifs)- and, possibly,
53 e members of a larger superfamily containing ITIM sequences, the inhibitory receptor superfamily (IRS
54 erefore, TLT1 represents a new costimulatory ITIM immunoreceptor and is the second ITIM-bearing recep
56 ic binding domain, or within its cytoplasmic ITIM, completely abolished PECAM-1-mediated cytoprotecti
58 the "conventional" 2DL4 with the cytoplasmic ITIM (2DL4.1) and two encoding different cytoplasmic tru
59 al, but opposite to KIR, the membrane-distal ITIM is of primary importance rather than the membrane-p
64 viding evidence that the ITIMs of other dual ITIM-containing receptors are also sequentially phosphor
65 inhibitory effect was mediated through dual ITIM recruitment of the SH2-containing protein tyrosine
66 enotypes and nonredundant functions for each ITIM-containing receptor in the context of platelet home
69 CD20 occurs independently of the FcgammaRIIb ITIM, indicating that signaling downstream of FcgammaRII
72 results suggest a cell biological basis for ITIM receptor signaling and establish an experimental fr
73 se results demonstrate a functional role for ITIM in the regulation of IL-4-induced proliferation.
81 four tyrosines, two of which are embedded in ITIM-signaling motifs (Y597 and Y667) and are likely inv
84 central to the initiation of both inhibitory ITIM and stimulatory ITAM signaling, the events that reg
85 of immunoreceptor tyrosine-based inhibitory (ITIM) motifs in the cytoplasmic domains of the inhibitor
88 ng the cytoplasmic tails containing the ITAM/ITIM motifs, leaving the remainder of the receptor intac
89 imulation by insulin via FcgammaRIIB and its ITIM, SHIP-1 activation, and resulting blunted activatio
90 BCR leads to tyrosine phosphorylation of its ITIM motifs and subsequent Src homology region 2 domain-
94 ain isoforms of these NK-cell receptors lack ITIM sequences and it has been proposed that these 'non-
97 expands the signaling potential of the large ITIM-receptor family and reveals an unsuspected componen
102 unoreceptor tyrosine-based inhibition motif (ITIM) in the gB cytoplasmic domain (gBcyt) and demonstra
103 unoreceptor tyrosine-based inhibition motif (ITIM) sequences in its cytoplasmic domain, which may be
105 unoreceptor tyrosine-based inhibition motif (ITIM) that, when phosphorylated, recruits the SH2-contai
106 unoreceptor tyrosine-based inhibition motif (ITIM), binds to the C-terminal Src homology 2 domain of
107 unoreceptor tyrosine-based inhibition motif (ITIM), inducing secretion of the suppressive cytokines I
108 unoreceptor tyrosine-based inhibition motif (ITIM), present in the cytoplasmic domain of Fc gammaRIIB
109 unoreceptor tyrosine-based inhibition motif (ITIM), which undergoes phosphorylation and is recognized
111 unoreceptor tyrosine-based inhibition motif (ITIM)-containing proteins, thereby suppressing phosphati
112 unoreceptor tyrosine-based inhibition motif (ITIM)-containing receptor, SIRPalpha (a member of the si
113 unoreceptor tyrosine-based inhibition motif (ITIM)-containing receptors have been shown to inhibit si
115 unoreceptor tyrosine-based inhibitory motif (ITIM) and an immunoreceptor tyrosine-based switch motif
117 unoreceptor tyrosine-based inhibitory motif (ITIM) containing molecule that belongs to the CD300 fami
118 unoreceptor tyrosine-based inhibitory motif (ITIM) family of inhibitory receptors, functions prominen
120 unoreceptor tyrosine-based inhibitory motif (ITIM) in the cytoplasmic domain, down-regulates humoral
121 unoreceptor tyrosine-based inhibitory motif (ITIM) known to mediate Fc gamma RIIB1 effects suggest th
122 unoreceptor tyrosine-based inhibitory motif (ITIM) of Ly49A that abolished the inhibitory function of
124 unoreceptor tyrosine-based inhibitory motif (ITIM) that binds and constitutively activates Shp2.
125 unoreceptor tyrosine-based inhibitory motif (ITIM) that, when appropriately engaged, becomes phosphor
127 unoreceptor tyrosine-based inhibitory motif (ITIM), which engages Src homology 2 (SH2) domain-contain
128 unoreceptor tyrosine-based inhibitory motif (ITIM), which is restricted to immature DCs (iDCs), monoc
129 unoreceptor tyrosine-based inhibitory motif (ITIM)-containing platelet endothelial cell adhesion mole
130 re immunoreceptor tyrosine inhibitory motif (ITIM)-containing proteins, and ITIM proteins CD22 and FC
131 unoreceptor tyrosine-based inhibitory motif (ITIM)-containing receptors inhibit cellular responsivene
132 unoreceptor tyrosine-based inhibitory motif (ITIM)-containing type I transmembrane protein belonging
134 unoreceptor tyrosine-based inhibitory motif (ITIM)-like domain and the tyrosine phosphatase Corkscrew
141 n a phosphatase recruiting inhibitory motif (ITIM); therefore, we conclude that CD200R represents a n
144 noreceptor tyrosine-based inhibition motifs (ITIM) within the cytoplasmic domain of CEACAM1 and the S
145 noreceptor tyrosine-based inhibitory motifs (ITIM) have been implicated in the negative modulation of
147 noreceptor tyrosine-based inhibitory motifs (ITIM) in their cytoplasmic domains, associate with mouse
149 noreceptor tyrosine-based inhibition motifs (ITIMs) have been described previously in two lineages of
150 noreceptor tyrosine-based inhibition motifs (ITIMs) have been shown to mediate inhibitory properties.
151 noreceptor tyrosine-based inhibition motifs (ITIMs), mediated by the crosslinking of BCR and FcgammaR
154 noreceptor tyrosine-based inhibitory motifs (ITIMs) control internalization of antibody bound to CD33
155 noreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic tail, classifying this protein
159 ring immunotyrosine-based inhibitory motifs (ITIMs) maintain natural killer (NK) cell tolerance to no
161 noreceptor tyrosine-based inhibitory motifs (ITIMs) of the -4L isoform, and associates with Src homol
162 noreceptor tyrosine-based inhibitory motifs (ITIMs) within its cytoplasmic domain, and co-ligation of
163 noreceptor tyrosine-based inhibitory motifs (ITIMs), only the two carboxyl-terminal ITIM tyrosines ar
170 elates with weak SHP-2 binding to the mutant ITIM of 2DL4 in NK cells and a corresponding nonphosphor
171 hese results show that, like KIR, both NKG2A ITIMs are required for mediating the maximal inhibitory
173 ctivity and production, and the noncanonical ITIM-containing receptor TREM-like transcript-1, which i
174 SHP-1 and SHP-2 through a new, nonclassical ITIM motif, (V/I/L)XpY(M/L/F)XP, which corresponds to th
178 lation is controlled by the accessibility of ITIM to tyrosine phosphatases and that KIR binding to HL
180 rt inclusion of PECAM-1 within the family of ITIM-containing inhibitors of PTK-dependent signal trans
181 ikely altered the expression and function of ITIM-bearing inhibitory receptors (Siglecs) that bind si
182 ion to interfering with the functionality of ITIM+ FcgammaR, effective anti-idiotypic and antitumoral
183 eared to conform to the established model of ITIM-mediated attenuation of ITAM-driven activation.
186 review, we discuss the diverse repertoire of ITIM-containing receptors in platelets, highlighting int
190 the identification of PECAM-1, several other ITIM-containing platelet receptors have been discovered.
193 and recruits SHP-2 through a phosphorylated ITIM, indicating a potential signaling function in effec
196 he N-terminal domain of CD37 in a predicted "ITIM-like" motif and mediates SHP1-dependent death, wher
197 esion molecule 1 (PECAM-1) as a prototypical ITIM-bearing receptor, we demonstrate that initiation of
198 ion of the tyrosine in the membrane-proximal ITIM abrogated the ability of KIR to block Ab-dependent
202 its association with DAP12, and the putative ITIM in the NKp44 cytoplasmic domain does not appear to
204 d by receptors that are not known to recruit ITIMs, we determined the effect of SHIP expression on co
205 ligand for the phosphorylated Fc gamma RIIB1 ITIM, although the SHP-2 decoy exhibits some ability to
206 latory ITIM immunoreceptor and is the second ITIM-bearing receptor to be identified in platelets afte
208 f these findings, we propose that sequential ITIM phosphorylation provides a general mechanism for pr
210 city responses; 2) the phosphorylated single ITIM recruits SHP-2 protein tyrosine phosphatase, but no
211 , mutation of the tyrosine within the single ITIM does not completely abolish inhibitory function; an
212 ow in human NK cell lines that 1) the single ITIM of 2DL4 efficiently inhibits natural cytotoxicity r
214 andem ITIMs of KIR3DL1 (3DL1) and the single ITIM of 2DL4 were directly compared in functional and bi
216 -interacting segment contains the C-terminal ITIM tyrosine and a serine residue that undergo activati
217 the prior phosphorylation of its C-terminal ITIM, providing evidence that the ITIMs of other dual IT
218 family kinases phosphorylate the C-terminal ITIM, thereby enabling phosphorylation of the N-terminal
220 tifs (ITIMs), only the two carboxyl-terminal ITIM tyrosines are required for efficient recruitment of
222 y enabling phosphorylation of the N-terminal ITIM of PECAM-1 by other Src homology 2 domain-containin
223 nally, the phosphorylation of the N-terminal ITIM of Siglec-9 by Csk is enhanced by the prior phospho
225 that this is an oversimplification, and that ITIM-containing receptors are versatile regulators of pl
226 studies using these approaches indicate that ITIM-containing receptors function at least in part by s
229 n the IL-4 signaling pathway, we ablated the ITIM of IL-4Ralpha by deletion and site-directed mutagen
232 to bind homophilically are required for the ITIM phosphorylation of CEACAM1 that is a prerequisite f
233 eered that lacked either the tyrosine in the ITIM or an arginine-tyrosine motif in the transmembrane
237 (XmAb5871) stimulated phosphorylation of the ITIM of FcgammaRIIb and suppressed BCR-induced calcium m
238 1/mu2 interaction, either by mutation of the ITIM tyrosines in 3DL1 or mutation of mu2, significantly
239 n sequential tyrosine phosphorylation of the ITIM, recruitment and phosphorylation of p145SHIP, and s
242 ls revealed that these processes require the ITIM (immunoreceptor tyrosine-based inhibition motif) of
243 ar activation potential, indicating that the ITIM does not influence 2DL4.1 activating function.
252 C-terminal ITIM, providing evidence that the ITIMs of other dual ITIM-containing receptors are also s
253 mplex with the inhibition dependent upon the ITIMs of CEACAM1 and Src homology 2 domain-containing ph
254 strate that the tyrosine residues within the ITIMs are phosphorylated and serve for the association a
259 in an NK-like cell line, we found that this ITIM-like motif from NKp44 lacks inhibitory capacity in
260 PAMPs, and competes with SHP-1/2 binding to ITIMs of cytokine receptors, thereby inhibiting signalin
263 28) is distinct and independent from the two ITIM tyrosines required for efficient SHP-1 recruitment
266 s of KIR2DL5, KIR3DL1 (a type I KIR with two ITIMs), and KIR2DL4 (the only other type II KIR, which h
269 rnalization, raising the question of whether ITIM phosphorylation plays any role in this process.
270 lation of cytosolic tyrosine residues within ITIMs results in recruitment of a protein tyrosine phosp
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