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1 PKC theta and 14-3-3 tau coimmunoprecipitated from Jurka
2 PKC-theta activation of NF-kappaB is mediated through th
3 PKC-theta acts directly or indirectly to stimulate phosp
4 PKC-theta and calcineurin are also partially responsible
5 PKC-theta is thus required for maximum up-regulation of
6 PKC-theta is thus required for promoting FasL expression
7 PKC-theta plays a central role in Teff cell activation a
8 PKC-theta specifically cooperates with calcineurin, and
9 PKC-theta then couples IkappaB kinases (IKKs) to the CBM
10 PKC-theta transduces the signal from the TCR through act
11 PKC-theta(-/-) murine platelets showed significantly low
12 PKC-theta(-/-) T cells had reduced activity of the AKT k
13 PKC-theta-deficient CD4(+) T cells show an impaired prol
14 PKC-theta-mediated activation of Bcl-xL reporter was inh
15 PKC-theta-mediated activation of the Stat3 promoter was
16 also accumulates in the immune synapse in a PKC theta-dependent manner upon antigen recognition by T
17 struct driven by two tandem -180 sites and a PKC-theta construct caused a significant increase in the
18 7 region of the IL-2 promoter/enhancer and a PKC-theta construct caused a similar increase in the rep
19 Th1 cell differentiation, whereas activated PKC-theta reverted only GATA3 transcription factor and t
20 ansfected wild-type or constitutively active PKC theta, as well as by endogenous PKC in ionomycin- an
28 ys confirmed the association of PKC beta and PKC theta with spectrin following its reorganization.
29 rologous cultures combining normal nerve and PKC theta-deficient muscle, as might be expected from th
30 APCs polymerize actin and organize talin and PKC theta normally, forming an immune synapse that is st
32 s study the potential roles of PKC-alpha and PKC-theta in MDR1 gene transcriptional regulation were e
35 iated coordinately by both Akt-dependent and PKC-theta-dependent signaling pathways in primary T cell
36 glycerol content and reduced PKC-epsilon and PKC-theta activity in liver and muscle respectively.
40 on of a kinase-deficient mutant or antisense PKC-theta selectively inhibits CD3-CD28 costimulation, b
43 re, all these molecules (spectrin, PKC beta, PKC theta, and receptor for activated C kinase-1) cotran
44 physical and functional interactions between PKC theta, a Ca(2+)-independent PKC enzyme which is expr
46 ognition by T cells and is phosphorylated by PKC theta at Ser-225, which is required for lipid raft t
47 P is phosphorylated in the immune synapse by PKC theta and thereby targeted to lipid rafts to temper
52 rtial T-cell activation that failed to cause PKC-theta translocation also failed to cause T-cell prol
53 is article, we show that purified, naive CD4 PKC-theta(-/-) T cells were defective in Th17 differenti
55 several PKC isoenzymes expressed in T cells, PKC-theta is unique in being rapidly recruited to the si
60 KC-theta activation via Vav-1, which couples PKC-theta to PI3-K and allows it to be phosphorylated.
61 vation in SAP-deficient cells, but decreased PKC-theta recruitment, Bcl-10 phosphorylation, IkappaB-a
64 f MKK4, suggesting that interferon-dependent PKC-theta activation regulates downstream engagement of
65 d that the TCR-derived signaling that drives PKC theta; membrane translocation requires the Src famil
69 ing that a SAP/Fyn-mediated pathway enhances PKC-theta/NF-kappaB1 activation and suggesting a role fo
71 G vesicle binding experiments with expressed PKC-theta and moesin demonstrate that both bind to vesic
74 nd association with CD28 to be essential for PKC-theta-mediated downstream signaling and the differen
77 ion, further demonstrating a requirement for PKC-theta in IFN-dependent transcriptional activation.
80 itiated NF-kappaB activation was absent from PKC-theta(-/-) mature T lymphocytes, but was intact in t
85 duced in the spleens of MOG(35-55)-immunized PKC theta-/- mice as well as in in vitro-stimulated CD4+
86 tion of splenic T lymphocytes from immunized PKC theta-/- mice revealed significantly reduced product
89 nd diminished joint pathology (p < 0.005) in PKC-theta-deficient compared with wild-type littermates.
90 on of a constitutively active form of AKT in PKC-theta(-/-) T cells restored the ability to inhibit i
91 constitutively active form of calcineurin in PKC-theta-/- Jurkat cells could readily overcome the abo
92 receptor was also significantly decreased in PKC-theta(-/-) mice compared with wild-type littermates.
94 ingly, the single and combined deficiency in PKC-theta or CARMA-1-the two signal transducers at the N
95 inhibit or promote iTreg differentiation in PKC-theta(-/-) T cells accordingly, indicating that the
96 nificantly increased Th17 differentiation in PKC-theta(-/-) T cells, suggesting that reduced Stat3 le
97 nduced iTreg differentiation was enhanced in PKC-theta(-/-) T cells or wild-type cells treated with a
105 3-3 tau also inhibited phorbol ester-induced PKC theta translocation from the cytosol to the membrane
106 on TCR stimulation and regulates TCR-induced PKC-theta activation via Vav-1, which couples PKC-theta
107 d the therapeutic implications of inhibiting PKC-theta in Teff cells, to reduce effector function, an
108 ast to adoptive transfer experiments, intact PKC-theta-/- mice displayed delayed, but successful card
109 , introgression of the Bcl2l1 transgene into PKC-theta null mouse failed to rescue NKT cell developme
111 e, we assessed whether one specific isoform, PKC-theta, was expressed in critical CNS regions that re
114 and T cells, is disrupted in T cells lacking PKC theta and in B and T cells lacking Bcl10, a caspase
115 TCR stimulation, peripheral T cells lacking PKC-theta; failed to activate NF-kappaB and AP-1, and to
117 Consistently, in murine platelets lacking PKC-theta, platelet aggregation and secretion were also
119 FN-activated STAT pathway, as siRNA-mediated PKC-theta knockdown had no effects on STAT1 phosphorylat
121 ity by overexpression of a dominant-negative PKC-theta mutant also blocked GAS-driven transcription,
124 ) inhibited Ca2+ influx in wild-type but not PKC-theta-/- T cells, suggesting that PKC-theta plays a
125 PKC isoforms, classical PKC alpha and novel PKC theta, have been shown to be enriched in skeletal mu
126 ver, the in vivo consequences of ablation of PKC theta on T cell function in inflammatory autoimmune
128 pathway in CD3/CD28-stimulated activation of PKC theta and NF-kappaB, and suggest that Vav-1 associat
130 ssion was dramatically reduced in the CNS of PKC theta-/- mice compared with wild-type mice during th
132 ing that 14-3-3 tau inhibits the function of PKC theta not only by preventing its translocation to th
133 These results underscore the importance of PKC theta in the regulation of multiple T cell functions
135 to investigate the potential involvement of PKC theta in the development of experimental autoimmune
136 14-3-3 tau caused increased localization of PKC theta in the particulate fraction in unstimulated ce
137 led to a diffuse pattern of localization of PKC theta; and lymphocyte function-associated antigen-1
141 PKC theta; or a dominant-negative mutant of PKC theta; failed to synergize with CN and did not incre
144 iacylglycerol, with subsequent activation of PKC-theta and inhibition of insulin signaling in muscle.
145 ncentrations, which results in activation of PKC-theta leading to increased IRS-1 Ser(307) phosphoryl
147 ion did not affect the catalytic activity of PKC-theta but inhibited the association of CD28 with PKC
148 owed a selective increase in the activity of PKC-theta, indicating that the translocated enzyme is ac
149 r, AICD as well as Fas-mediated apoptosis of PKC-theta(-/-) T cells were restored in the presence of
162 e examined whether mice with inactivation of PKC-theta are protected from fat-induced insulin resista
164 NF-kappaB activation, whereas inhibition of PKC-theta and PKC-zeta inhibited IL-1beta-stimulated act
166 ination with other treatments, inhibition of PKC-theta may facilitate achieving long-term survival of
172 small interfering RNA-mediated knockdown of PKC-theta in Jurkat cells also resulted in apoptosis upo
174 or the immunological synapse localization of PKC-theta and indicate V3-based 'decoys' may be therapeu
176 by oral gavage increased the localization of PKC-theta to cell membranes in the hypothalamus, which w
177 ression of a constitutively active mutant of PKC-theta potently induces NF-kappaB activation and stim
178 e II (gamma) IFNs induced phosphorylation of PKC-theta in human T-cell lines and primary human T-lymp
180 induced marked calcium flux, recruitment of PKC-theta and F-actin to the cell/bead contact site, and
182 t CARMA1(L808P), restores the recruitment of PKC-theta, Bcl10, and IKKbeta into lipid rafts in CARMA1
184 These findings suggest that the role of PKC-theta in outside-in signaling following engagement o
187 R-proximal signaling and that sumoylation of PKC-theta is essential for the formation of a mature imm
189 ility complex (MHC) induces translocation of PKC-theta to membrane lipid rafts, which localize to the
192 lack constitutive expression of PKC-alpha or PKC-theta at detectable levels were transfected with ful
194 ad, Bid, Akt1, Akt2, PKC-mu, PKC-epsilon, or PKC-theta was achieved by transient transfection using s
198 ial molecular mediator to integrate positive PKC-theta-dependent TCR signals to induce peak RORgammat
203 e results suggest that innervation regulates PKC theta and alpha isoform expression in skeletal muscl
204 F6, as well as upstream NF-kappaB regulators PKC theta, CARMA1, Bcl-10, and MALT1, which connect to t
205 cell receptor (TCR) crosslinking in the same PKC-theta-/- T cells did result in significantly decreas
208 s or wild-type cells treated with a specific PKC-theta inhibitor, but was inhibited by the PKC-theta
210 KC-dependent signals and, more specifically, PKC theta-mediated functions during T-cell activation.
211 e shown that in response to TCR stimulation, PKC-theta-/- T cells undergo apoptosis due to greatly re
212 ive than wild-type 14-3-3 tau in suppressing PKC theta-dependent IL-2 promoter activity, suggesting t
213 on of SAP in T cells increased and sustained PKC-theta recruitment to the immune synapse and elevated
215 oduction, and, conversely, membrane-targeted PKC-theta mutants rescued IL-4 expression in SAP(-/-) CD
217 es to the immunologic synapse indicated that PKC theta;, unlike TCR, persisted in the synapse for at
220 Collectively, our results demonstrate that PKC-theta deficiency results in an attenuated response t
222 In conclusion, our findings demonstrate that PKC-theta is a crucial component mediating fat-induced i
223 Altogether, these findings demonstrate that PKC-theta is an interferon-inducible kinase and strongly
227 (+) T cells, providing genetic evidence that PKC-theta is a critical component of SLAM/SAP-mediated p
229 tion and immunohistochemistry, we found that PKC-theta was expressed in discrete neuronal populations
230 odels of Ag-induced arthritis and found that PKC-theta-deficient mice develop disease, but at a signi
236 mputerized tomographic imaging revealed that PKC-theta deficiency also protects from bone destruction
238 sistance in skeletal muscle and suggest that PKC-theta is a potential therapeutic target for the trea
239 h studies in T-cell lines had suggested that PKC-theta regulates activation of the JNK signalling pat
240 ut not PKC-theta-/- T cells, suggesting that PKC-theta plays a role in PMA-mediated inhibition of Ca2
241 P-1 and IkappaB kinase-beta, suggesting that PKC-theta stimulates Stat3 transcription via the AP-1 an
242 cardiac allograft rejection, suggesting that PKC-theta-regulated survival is required for T cell-medi
244 KC-theta inhibitor, but was inhibited by the PKC-theta activator PMA, or by CD28 crosslinking, which
247 articular cartilage damage were mild in the PKC-theta-deficient mice as compared with wild-type mice
249 , Zap70, Vav, and PI3K expression, and their PKC theta- and JNK-regulated expression/activation.
250 ich in turn recruits protein kinase C theta (PKC theta) and Bcl10 to the microdomains, causing subseq
253 lymphocytes requires protein kinase C theta (PKC-theta) and an appropriately elevated free intracellu
255 ) signaling molecule protein kinase C theta (PKC-theta)-mediated phosphorylation of SRC1 is important
260 We now show that protein kinase C-theta (PKC-theta), a novel PKC isoform, plays a central role in
261 , the recruitment of protein kinase C-theta (PKC-theta), Bcl10, and IkappaB kinase beta (IKKbeta) int
262 se cascade involving protein kinase C-theta (PKC-theta), leading to defects in insulin signaling and
263 at in the absence of protein kinase C-theta (PKC-theta), superantigen (staphylococcal enterotoxin B)-
266 nant active mutant of protein kinase C theta(PKC theta) induced strong SMRT-receptor interaction in t
267 , which localize to the T cell synapse; this PKC-theta translocation is important for its function.
268 or-dependent transactivation in part through PKC theta-dependent enhancement of SMRT-receptor interac
274 physiological T cell activation translocates PKC-theta to rafts, which localize to the T cell synapse
276 hed with palmitic acid, are CNS mediated via PKC-theta activation, resulting in reduced insulin activ
278 analysis, was significantly higher, whereas PKC-theta, -eta, and -mu were significantly lower in mus
283 Although the molecular interactions in which PKC-theta; engages have not been fully delineated, insig
286 a but inhibited the association of CD28 with PKC-theta and filamin A and impaired the assembly of a m
287 Fyn recruitment, yet SAP's interactions with PKC-theta occurred independent of phosphotyrosine bindin
288 y reduced in human platelets pretreated with PKC-theta RACK peptide, which may contribute to the lowe
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