The NFAT family of transcription factors include the cytoplasmic NFAT transcription factors [NFATc1 (NFATc), NFATc2 (NFATp), NFATc3 (NFAT4, NFATx), NFATc4 (NFAT3), NFATc5] and nuclear NFAT (NFATn ...
The NFAT family of transcription factors include the cytoplasmic NFAT transcription factors [NFATc1 (NFATc), NFATc2 (NFATp), NFATc3 (NFAT4, NFATx), NFATc4 (NFAT3), NFATc5] and nuclear NFAT (NFATn ...
The MAPKs are important transducers of growth and stress stimuli in virtually all eukaryotic cell types. In the mammalian heart, MAPK signaling pathways have been hypothesized to regulate myocyte growth in response to developmental signals or physiologic and pathologic stimuli. Here we generated cardiac-specific transgenic mice expressing dominant-negative mutants of p38α, MKK3, or MKK6. Remarkably, attenuation of cardiac p38 activity produced a progressive growth response and myopathy in the heart that correlated with the degree of enzymatic inhibition. Moreover, dominant-negative p38α, MKK3, and MKK6 transgenic mice each showed enhanced cardiac hypertrophy following aortic banding, Ang II infusion, isoproterenol infusion, or phenylephrine infusion for 14 days. A mechanism underlying this enhanced-growth profile was suggested by the observation that dominant-negative p38α directly augmented nuclear factor of activated T cells (NFAT) transcriptional activity and its nuclear translocation. In ...
The present study investigated the role of NFATc in p300- and ET-1-induced transcription of the gene encoding an antiapoptotic molecule, bcl-2, in cardiac myocytes. We showed here that mutation of NFAT sites within the bcl-2 promoter completely abolished both p300- and ET-1-responsive bcl-2 transcription in cardiac myocytes, suggesting a critical role of NFATc in these processes. To date, 5 NFAT isoforms have been identified and designated NFATc1 (also known as NFAT2 or NFATc), NFATc2 (NFAT1 or NFATp), NFATc3 (NFAT4 or NFATx), NFATc4 (NFAT3), and NFAT5. Among these, only NFAT5 appears to be constitutively nuclear and not to be regulated by calcineurin.27 NFATc1-NFATc4 bind the consensus DNA sequence through a Rel homology domain, and all 4 of these factors are expressed in cardiac myocytes.11 The present study demonstrated that NFATc1 binds to the NFAT site within the bcl-2 promoter in a sequence-specific manner. We also demonstrated that p300 acts as a coactivator of NFATc1 in the transcription ...
This study found that compounds exhibiting antioxidant properties, i.e., NAC, PBN, and lipoic acid, prevent ANG II from activating the transcription factor NFAT3 in cardiomyocytes. Consistent with the hypothesis that oxidants mediate NFAT3 activation, we found that H2O2 induces activation of NFAT3 transcription factor in a narrow dose range (50-150 μM) within 1-8 h. A chemical inhibitor of ERKs, PD98059, inhibited H2O2 from activating NFAT3. In contrast, the PI3K inhibitor LY249002 and the p38 MAPK inhibitor SB202190 failed to show an inhibitory effect on H2O2-induced NFAT3 activation. A dominant negative form of c-Jun, TAM67, abolished NFAT3 activation. Because PD98059 inhibits the activation of AP-1 transcription factors by H2O2 (46), our data suggest a role of AP-1 downstream of ERKs in the H2O2-induced NFAT3 activation in cardiomyocytes.. Cooperation of NFATs with other families of transcription factors is an important character of NFATs in regulating gene expression. There is evidence that ...
The NFAT family of transcription factors has been strongly implicated in the T cell activation-dependent regulation of numerous cytokine genes and is therefore believed to play a pivotal role in the TCR-induced expression of cytokine genes during Th cell differentiation (3, 4, 5). While the NFAT signaling pathway is known to be exquisitely sensitive to changes in the [Ca2+]i (6, 7, 12), which is believed to play an important role in coupling differences in TCR-induced signaling events into changes in gene expression, the role of spatiotemporally distinct patterns of NFAT signaling in the regulation of specific cytokine genes is not well understood. In the current study, we have used an efficient retroviral delivery system to introduce a calcineurin-independent, constitutively active mutant version of NFATc1 (caNFATc1) into primary murine CD4+ T cells, thereby allowing us to examine the functional consequences of sustained NFAT activity on gene expression in primary T cells.. While we found that ...
Plasmid NFAT/AP-1 3x luciferase from Dr. Anjana Raos lab contains the insert NFAT/AP-1 3x and is published in EMBO J. 2000 Sep 1. 19(17):4783-95. This plasmid is available through Addgene.
The biological mechanisms that sculpt the fine structure of the adult brain and their alterations in neurodegenerative diseases remain largely unknown. In this report we demonstrated that Aβ neurotoxic damage can be prevented or even reversed by inhibiting calcineurin-mediated activation of NFAT. Importantly, the same profound morphological changes occur when a constitutively active form of the transcription factor NFAT is introduced. The results are consistent with the hypothesis that the neurotoxic effects of Aβ are mediated, at least in part, by the transcriptional activation of NFAT downstream target genes. Although the contribution of NFAT to neurological function or dysfunction has received little attention, recent findings have demonstrated a role of NFAT in synaptic plasticity during development (Nguyen and Di Giovanni, 2008; Schwartz et al., 2009). Moreover, NFAT shows an abnormal nuclear accumulation in the brains of AD patients (Wu et al., 2010), which directly correlates with the ...
human NF-IL4 protein: a interleukin-4 (IL-4)-dependent transcription factor sharing a DNA-binding motif with the interferon-gamma induced nuclear binding factor; binds to specific element IL-4RE
Full text for this publication is not currently held within this repository. Alternative links are provided below where available. ...
Researchers in the Department of Physiology, Anatomy and Genetics publish in the prestigious Molecular Cell an article entitled Distinct Spatial Ca2+ Signatures Selectively Activate Different NFAT Transcription Factor Isoforms
Sigma-Aldrich offers abstracts and full-text articles by [Jakob Voelkl, Ioana Alesutan, Tatsiana Pakladok, Robert Viereck, Martina Feger, Sobuj Mia, Tanja Schönberger, Angelika A Noegel, Meinrad Gawaz, Florian Lang].
NFAT1 (NFATc2), 0.1 ml. Nuclear factor of activated T cells (NFAT) is a family of transcription factors implicated in multiple biological processes including cytokine gene expression, cardiac hypertrophy and adipocyte differentiation.
Inflammation, in excess, was believed to be an underlying factor in the pathogenesis of proliferative cardiovascular diseases such as atherosclerosis and resten...
Plasmid pGL3-NFAT luciferase from Dr. Jerry Crabtrees lab contains the insert 3x NFAT binding sequence and is published in Nature. 1992 Jun 25. 357(6380):695-7. This plasmid is available through Addgene.
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
GFP(蛍光蛋白質)、Luc(ルシフェラーゼ)を用いた共鳴エネルギー移動原理によるバイオセンサは、イオン濃度測定、 情報伝達分子の活性測定など、様々な細胞内情報伝達を測定するツールとして利用されています。FDSS/μCELL は、 高感度2次元センサ(カメラ)と波長切り替え装置を用いることで、発光をベースとするBRET(生物発光共鳴エネルギー 移動)や蛍光をベースとするFRET(蛍光共鳴エネルギー移動)をマイクロプレート一括で測定できます ...
Vodacom may hurt its profitability in the short term with a new 79 cents per minute prepaid call rate but it is smaller rival ...
NFAT1小鼠单克隆抗体[25A10.D6.D2] - ChIP Grade(ab2722)可与小鼠, 大鼠, 人样本反应并经WB, IP, IHC, ICC, GSA, Flow Cyt, ChIP…
In this study, we used whole-genome array analysis and pharmacological reagents to identify PROCR as a potential Cn/NFAT-dependent gene in vascular smooth muscle. We corroborate the only report to date that vascular SMCs do express the protein C receptor (PROCR).15 More importantly, we validate our informatics approach and are the first to report Cn/NFAT signaling as a regulator of PROCR activation. We show PDGF-BB stimulation induced PROCR expression in a Cn/NFAT-dependent manner at both the transcriptional and translational levels. Mutation of a highly conserved NFAT binding motif significantly attenuated PROCR promoter activation, supporting the NFAT-dependent property of PROCR activity. In addition, PROCR expression is upregulated in vivo as a result of acute vascular injury, highlighting the potential role of PROCR in vessel restenosis.. Until the recent detection of PROCR in vascular SMCs, PROCR was believed to be expressed predominantly in ECs. Studies to date on PROCR transcription focus ...
In this study, we demonstrate for the first time that changes in blood glucose levels are readily detected by NFATc3 in arterial smooth muscle in vivo and that the calcineurin/NFATc3 signaling pathway regulates the expression of OPN, which is a key player in the development of vascular disease. Our major findings are as follows: (1) changes in extracellular glucose activate NFATc3 signaling in vivo; (2) NFATc3 has the ability to bind to at least one NFAT binding site (site 3) in the mouse promoter region of OPN; (3) NFATc3 activation leads to increased OPN mRNA and protein expression in intact arteries; (4) glucose-induced OPN expression is dependent on the release of extracellular nucleotides acting on P2Y membrane receptors; (5) glucose-induced OPN expression is prevented by pharmacological inhibition of calcineurin/NFAT signaling; and (6) STZ-induced diabetes increases OPN expression in the ascending and thoracic aorta, vascular segments particularly prone to atherosclerosis in diabetic ...
Calcium-dependent, calmodulin-stimulated protein phosphatase which plays an essential role in the transduction of intracellular Ca(2+)-mediated signals. Dephosphorylates and activates transcription factor NFATC1. Dephosphorylates and inactivates transcription factor ELK1. Dephosphorylates DARPP32.
PubMed comprises more than 30 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
TY - JOUR. T1 - Stat6 inhibits human interleukin-4 promoter activity in T cells. AU - Georas, S. N.. AU - Cumberland, J. E.. AU - Burke, T. F.. AU - Chen, R.. AU - Schindler, U.. AU - Casolaro, V.. PY - 1998/12/15. Y1 - 1998/12/15. N2 - The differentiation of naive T-helper (Th) cells into cytokine-secreting effector Th cells requires exposure to multiple signals, including exogenous cytokines. Interleukin-4 (IL-4) plays a major role in this process by promoting the differentiation of IL-4-secreting Th2 cells. In Th2 cells, IL- 4 gene expression is tightly controlled at the level of transcription by the coordinated binding of multiple transcription factors to regulatory elements in the proximal promoter region. Nuclear factor of activated T cell (NFAT) family members play a critical role in regulating IL-4 transcription and interact with up to five sequences (termed P0 through P4) in the IL-4 promoter. The molecular mechanisms by which IL-4 induces expression of the IL-4 gene are not known, ...
Nuclear factor of activated T-cells, cytoplasmic 2 is a protein that in humans is encoded by the NFATC2 gene. This gene is a member of the nuclear factor of activated T cells (NFAT) family. The product of this gene is a DNA-binding protein with a REL-homology region (RHR) and an NFAT-homology region (NHR). This protein is present in the cytosol and only translocates to the nucleus upon T cell receptor (TCR) stimulation, where it becomes a member of the nuclear factors of activated T cells transcription complex. This complex plays a central role in inducing gene transcription during the immune response. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. NFAT transcription factors are implicated in breast cancer, more specifically in the process of cell motility at the basis of metastasis formation. Indeed, NFAT1 (NFATC2) is pro-invasive and pro-migratory in breast carcinoma. To increase cell motility NFAT1 up-regulates the gene of the Lipocalin 2 ...
Paper III: Syndecan-4 is essential for development of concentric myocardial hypertrophy via stretch-induced activation of the calcineurin-NFAT pathway Alexandra V. Finsen, Ida G. Lunde, Ivar Sjaastad, Even K. Østli, Marianne Lyngra, Hilde O. Jarstadmarken, Almira Hasic, Ståle Nygård, Sarah A. Wilcox-Adelman, Paul F. Goetinck, Torstein Lyberg, Biljana Skrbic, Geir Florholmen, Theis Tønnessen, William E. Louch, Srdjan Djurovic, Cathrine R. Carlson, Geir Christensen. PLoS One, 2011 Dec 02. Published under the terms of the Creative Commons Attribution License. The published version of this paper is available at: https://doi.org/10.1371/journal.pone.0028302 ...
Background: Activation of the protein phosphatase calcineurin is a fundamental signaling event promoting hypertrophic growth and pathological remodeling of the heart. The modulatory calcineurin-interacting protein 1 (MCIP1) is an endogenous feedback inhibitor of calcineurin. We have previously shown that increasing the level of MCIP1 protein protects the heart from unrestrained activation of calcineurin, suggesting that strategies to increase MCIP1 protein in the heart may be a viable therapeutic approach. To this end we have undertaken genetic and biochemical studies to decipher mechanisms that regulate degradation of MCIP1 proteins.. Methods and Results: There are two major isoforms of MCIP1 (MCIP1.1 and MCIP1.4). MCIP1.1 levels are extremely stable with a half-life of over 8 hours in cultured cardiomyocytes. In contrast, MCIP1.4 levels are very low in an unstressed heart but increase precipitously in response to stress and calcineurin activation. Unlike MCIP1.1, the MCIP1.4 protein is ...
A processing block 2 is composed of a base 5 , where an upper substrate 6 formed with a metal material M and a lower substrate 7 formed with the metal material M or a ceramic material E are adhered, and cells C . . . supported by this base 5 ; and the cells C . . . are secured to the upper substrate 6 and/or the lower substrate 7 at least via cell positioners 6 s . . . established in the upper substrate 6 for positioning the cells C . . . , respectively. At the same time, at least the thickness Ld of regions Xc . . . situated under the cells C . . . in the lower substrate 7 is selected to be 1.0 [mm] or thinner, and, a thermo-module(s) comes into contact with the lower surface of the base 5.
On Thursday 29 June 2017, to mark the end of Youth Month, the Right2Know Campaign in KZN will march on Cell C in Durban to demand a reduction in the costs of data. This follows similar marches on MTN and Vodacom on World Press Freedom Day this year, and on the International Right2Know Day in 2016 respectively. It is particularly worthwhile to note that young people continue to suffer from the high cost of communication - a major issue when it comes to their right to access information and freedom of expression. The march is meant to amplify R2Ks call on telecommunications companies to stop ripping off the people of South Africa and bring down the cost of communications, as well as for ICASA (the regulator) to take regulatory action to force these corporates to bring down costs. In light of parliaments failure to rein in the profiteering companies, R2K resolves to continue exerting non-violent direct action on the cellphone companies until the costs of data have fallen.. Whilst Section 161b. of ...
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Expression of NFATC1 (NF-ATC, NFAT2, NFATc) in cancer tissue. The cancer tissue page shows antibody staining of the protein in 20 different cancers.
Calcineurin-mediated dephosphorylation of Drp1 contributes to mitochondrial phenotypes related to loss of PINK1.(A) Calcineurin enzyme activity was measured in
Rabbit polyclonal antibody raised against synthetic peptide of NFATC4. A synthetic peptide corresponding to residues surrounding S676 of human NFATC4. (PAB18192) - Products - Abnova
View mouse Nfatc3 Chr8:106058840-106130537 with: phenotypes, sequences, polymorphisms, proteins, references, function, expression
Gentaur molecular products has all kinds of products like :search , Prospecbio \ Mouse Anti Human Nuclear factor of activated T-cells cytoplasmic 1 NFATC1 \ ant-436 for more molecular products just contact us
Immunological karma: T cells reactive to old flu infections make un...The authors found that in patients with IM memory CD8+ T cells speci...Overall this demonstration of cross-reactivity involving 2 immunodomi... TITLE: Cross-reactive influenza virusspecific CD8+ T cells c... AUTHOR CONTACT: Liisa Selin University of Massa...,JCI,table,of,contents:,November,23,2005,biological,biology news articles,biology news today,latest biology news,current biology news,biology newsletters
FHL1 forms a complex with NFATc1. (A) GST-FHL1, GST-GATA-2, or GST and His-NFATc1 or His were coexpressed as indicated in E. coli. GST proteins and associated p
That looks really good. Is there a way to extract the values (rather than count them) and place the results in column C?. For example:. Cell B3 ("jj,oo,pp"). In column C3, it returns "2" as 2 of the values in cell B3 were found in column A. However, I am after which 2 values were found in column A. i.e. I am after a formula that returns "jj,pp") in cell c3 rather than "2". is this possible ...
If you just want to count the cells above or below a certain value, in this case, I want to count the cells above number 50.. Select a blank cell, for instance, the Cell C6, type this formula =COUNTIF(A1:C5,",50 ") (the range A1: C5 indicates the range you want to count the cells above the specified value of 50, the number 50 stands the criterion, you can change them as you need), and press Enter button on the keyboard. See screenshot:. ...
TY - JOUR. T1 - Eriodictyol Inhibits RANKL-Induced Osteoclast Formation and Function Via Inhibition of NFATc1 Activity. AU - Song, Fangming. AU - Zhou, Lin. AU - Zhao, J.. AU - Liu, Q.. AU - Yang, Mingli. AU - Tan, R.. AU - Xu, J.. AU - Zhang, G.. AU - Quinn, J.M.W.. AU - Tickner, Jennifer. AU - Huang, Y.. AU - Xu, Jiake. PY - 2016/9. Y1 - 2016/9. N2 - © 2016 Wiley Periodicals, Inc. Receptor activator of nuclear factor kappa-B ligand (RANKL) induces differentiation and function of osteoclasts through triggering multiple signaling cascades, including NF-?B, MAPK, and Ca2+-dependent signals, which induce and activate critical transcription factor NFATc1. Targeting these signaling cascades may serve as an effective therapy against osteoclast-related diseases. Here, by screening a panel of natural plant extracts with known anti-inflammatory, anti-tumor, or anti-oxidant properties for possible anti-osteoclastogenic activities we identified Eriodictyol. This flavanone potently suppressed ...
In most models of pathological hypertrophy studied to date, inhibition of calcineurin-NFAT signaling has yielded either a reduction in the hypertrophic response and/or a delay in the progression from hypertrophy to heart failure.9,38 The data presented in this study extend this paradigm to demonstrate that calcineurin-NFAT signaling is activated in a sustained manner during both TAC-induced pressure overload and myocardial infarction-induced heart failure. However, very little is presently known regarding the role of calcineurin-NFAT signaling in regulating physiological hypertrophy or adaptive growth of the myocardium. Our results indicate that calcineurin-NFAT is not activated after either voluntary wheel-running or swimming, despite the observation of significant cardiac hypertrophy. In fact, swimming exercise even produced a significant and reproducible reduction in NFAT-luciferase activity in the heart at certain time points. Also of note, direct infusion of GH-IGF-1, which is thought to ...
Identification of Nedd9 as a TGF-β-Smad2-3 Target Gene Involved in RANKL-Induced Osteoclastogenesis by Comprehensive Analysis. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Our results demonstrate that overexpression of mCAT protects mice from cardiac aging, providing direct evidence for the role of mitochondrial ROS in the aging of this vital organ. Several lines of evidence support this conclusion. In WT mice from the longevity cohort, we found age-dependent LV hypertrophy and a decline in cardiac performance (especially diastolic function), concomitant with the accumulation of oxidized mitochondrial proteins, mtDNA mutations, increased ventricular fibrosis, cardiomyocyte hypertrophy, a decline in SERCA2 protein, and activation of the calcineurin-NFAT pathway in the aged heart. These age-related alterations took place in the absence of significant cardiovascular risks such as diabetes, hypertension, or hypercholesterolemia, suggesting that these findings are primary changes of cardiac aging rather than secondary to other diseases. mCAT littermates were partially protected from all of the above age-related cardiac alterations, suggesting that these aging changes ...
Hypertrophy can be an adaptive response that allows organs to meet up increased functional needs appropriately. missing a catalytic subunit of Cn (CnA?/? or CnA?/?), we discovered that high blood sugar activates CnA selectively, whereas CnA is dynamic constitutively. Furthermore, CnA however, not CnA mediates hypertrophy. Next, we discovered that chronic reactive air species era in response to high blood sugar is normally attenuated in CnA?/? cells, recommending that Cn is normally of Nox upstream. In keeping with this, lack of CnA reduces basal blocks and appearance great blood sugar induction of Nox2 and Nox4. Inhibition of nuclear aspect of turned on T cells (NFAT), a CnA-regulated transcription aspect, reduces Nox2 and Nox4 appearance, whereas NFAT overexpression boosts Nox4 and Nox2, indicating that the CnA/NFAT pathway modulates Nox. These data reveal which the CnA/NFAT pathway regulates Nox and has an important function in high glucose-mediated hypertrophic replies in the kidney. ...
Here, we present several novel important findings as follows: First, activation of CD137 signaling induces NFATc1 expression and promotes angiogenesis in vivo, in vitro, and ex vivo. Second, CD137 signaling regulates phosphorylation of Smad1/5 and NFATc1 expression in ECs. Silencing of Smad1/5 attenuates the expression of NFATc1 and angiogenesis in vitro induced by CD137 signaling. Suppressing NFATc1 gene could inhibit angiogenesis induced by CD137 signaling in vitro. Therefore, CD137 signaling regulates angiogenesis by modulating Smad1/5‐NFATc1 signaling.. Atherosclerosis, a disease of chronic inflammation, is the primary cause of heart disease and stroke. As an important member of the TNFR superfamily, CD137‐CD137L interaction promotes inflammation. Evidence suggests that activation of CD137‐CD137L signaling may be a significant triggering event for the process of forming atherosclerotic plaque, and contributes to the plaque vulnerability.4 However, whether activation of CD137 has the ...
In this study, we identified a novel class of CRAC channel blockers using high-throughput chemical library screen and asked how inhibition of Ca2+ signaling during TCR stimulation influenced differentiation and effector functions of T cells in vitro and in vivo. Using a combination of NFAT translocation as readout and a cell line harboring amplified CRAC currents, we identified a novel class of immunomodulators, compound 5, and its analogs. A more potent analog of the lead compound, compound 5D, blocked CRAC currents generated by WT Orai1 and a constitutively active mutant of Orai1 without affecting Orai1 and STIM1 translocation, indicating that the blocking mechanism directly involves the pore-forming subunit, Orai1. Further studies of CRAC current inhibition showed block by extracellular, but not intracellular, application of compound 5D, suggesting that the binding site is accessible only from the extracellular face of Orai1. Comprehensive mutational analysis of all the residues with possible ...
AID fragments, derived from the autoinhibitory domain of the calcineurin A subunit were the first examined inhibitory peptides for calcineurin. These peptides, containing the residues 424-521 (AID 424-521 ), are potent inhibitors of the phosphatase activity by blocking the access of protein substrates to the catalytic centre of calcineurin [164]. A peptide spanning the residues 457-482 (AID 457-482 ) of calcineurin represents the core inhibitory motif [165, 166]. This peptide is already able to suppress the dephosphorylation of the RII phosphopeptide in phosphatase assays. However, additional autoinhibitory elements are present within the calcineurin region 420-457. Therefore, the peptides containing the extended AID region AID420-511 and AID328-511 were three- to fourfold more potent to inhibit RII phosphopeptide dephosphorylation compared to the AID457-482 peptide [167]. The 11R-AID457-482 peptide, containing eleven arginine residues, is reported to be indeed cell-permeable for selected cell ...
Sustained calcium signaling induces a state of anergy or antigen unresponsiveness in T cells, mediated through calcineurin and the transcription factor NFAT. We show here that Ca(2+)-induced anergy is a multistep program that is implemented at least partly through proteolytic degradation of specific signaling proteins. Calcineurin increased mRNA and protein of the E3 ubiquitin ligases Itch, Cbl-b and GRAIL and induced expression of Tsg101, the ubiquitin-binding component of the ESCRT-1 endosomal sorting complex. Subsequent stimulation or homotypic cell adhesion promoted membrane translocation of Itch and the related protein Nedd4, resulting in degradation of two key signaling proteins, PKC-theta and PLC-gamma1. T cells from Itch- and Cbl-b-deficient mice were resistant to anergy induction. Anergic T cells showed impaired calcium mobilization after TCR triggering and were unable to maintain a mature immunological synapse, instead showing late disorganization of the outer ring containing lymphocyte
Nfatc2 - Nfatc2 (Myc-DDK-tagged) - Mouse nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2 (Nfatc2), transcript variant 2 available for purchase from OriGene - Your Gene Company.
The antigen receptors of T and B cells recognize not only antigens derived from pathogenic cells and organisms, but also self-antigens expressed on the bodys own tissues. In healthy individuals, self-antigens do not elicit a significant immune response. Self-reactive lymphocytes are clonally eliminated during development and cells that survive this process are rendered tolerant in the periphery. One of the mechanisms responsible for peripheral lymphocyte tolerance is anergy, an intracellular process in which antigen receptors become un-coupled from their downstream signaling pathways. Anergic lymphocytes remain in a state of non-responsiveness that prevents harmful responses to self-tissues. NFAT proteins play a central role in tolerance induction in T cells. Using both ex-vivo and mice models, we have shown that tolerant T cells express a novel set of anergy-associated genes, distinct from those characteristics of a productive immune response. The expression of those genes is NFAT-dependent ...