Preferential Activation of Nuclear Factor of Activated T Cells c Correlates with Mouse Strain Susceptibility to Allergic Responses and Interleukin-4 Gene Expression

2001 ◽  
Vol 24 (1) ◽  
pp. 58-65 ◽  
Author(s):  
Judith Clancy Keen ◽  
Lynette Sholl ◽  
Marsha Wills-Karp ◽  
Steve N. Georas
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Mouse Strain ◽  
Interleukin 4 ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Preferential Activation

scholarly journals STIM2 targets Orai1/STIM1 to the AKAP79 signaling complex and confers coupling of Ca2+entry with NFAT1 activation

2020 ◽  
Vol 117 (28) ◽  
pp. 16638-16648 ◽  
Author(s):  
Ga-Yeon Son ◽  
Krishna Prasad Subedi ◽  
Hwei Ling Ong ◽  
Lucile Noyer ◽  
Hassan Saadi ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Unique Role ◽  
Signaling Complex ◽  
Contact Sites ◽  
Channel Function

The Orai1 channel is regulated by stromal interaction molecules STIM1 and STIM2 within endoplasmic reticulum (ER)-plasma membrane (PM) contact sites. Ca2+signals generated by Orai1 activate Ca2+-dependent gene expression. When compared with STIM1, STIM2 is a weak activator of Orai1, but it has been suggested to have a unique role in nuclear factor of activated T cells 1 (NFAT1) activation triggered by Orai1-mediated Ca2+entry. In this study, we examined the contribution of STIM2 in NFAT1 activation. We report that STIM2 recruitment of Orai1/STIM1 to ER-PM junctions in response to depletion of ER-Ca2+promotes assembly of the channel with AKAP79 to form a signaling complex that couples Orai1 channel function to the activation of NFAT1. Knockdown of STIM2 expression had relatively little effect on Orai1/STIM1 clustering or local and global [Ca2+]iincreases but significantly attenuated NFAT1 activation and assembly of Orai1 with AKAP79. STIM1ΔK, which lacks the PIP2-binding polybasic domain, was recruited to ER-PM junctions following ER-Ca2+depletion by binding to Orai1 and caused local and global [Ca2+]iincreases comparable to those induced by STIM1 activation of Orai1. However, in contrast to STIM1, STIM1ΔK induced less NFAT1 activation and attenuated the association of Orai1 with STIM2 and AKAP79. Orai1-AKAP79 interaction and NFAT1 activation were recovered by coexpressing STIM2 with STIM1ΔK. Replacing the PIP2-binding domain of STIM1 with that of STIM2 eliminated the requirement of STIM2 for NFAT1 activation. Together, these data demonstrate an important role for STIM2 in coupling Orai1-mediated Ca2+influx to NFAT1 activation.

scholarly journals Identification of cis-acting regulatory elements controlling interleukin-4 gene expression in T cells: roles for NF-Y and NF-ATc.

1993 ◽  
Vol 13 (8) ◽  
pp. 4793-4805 ◽  
Author(s):  
S J Szabo ◽  
J S Gold ◽  
T L Murphy ◽  
K M Murphy
Keyword(s):  
T Cells ◽  
T Cell ◽  
Promoter Activity ◽  
Regulatory Elements ◽  
Interleukin 4 ◽  
Specific Factor ◽  
Gene Promoters ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Cis Acting

Activity of the murine interleukin-4 (IL-4) promoter was localized to several cis-acting elements present within the first 300 bp from the transcriptional initiation site. Five repeated elements, P0 to P4, that share the common consensus ATTTTCCNNT were located between -40 and -250, and each was shown to interact with the T-cell-specific factor NF(P). These distinct P sites appear functionally interchangeable and cooperatively confer cyclosporin A-sensitive and ionomycin-inducible promoter activity. NF(P) may be closely related to the cytoplasmic component of NF-AT (nuclear factor of activated T cells), a T-cell-specific factor essential for IL-2 gene transcription, as judged from indistinguishable molecular weights and protease fragmentation patterns of UV-photolabeled factors. Also, we identified an element in the IL-4 promoter with homology to the Y box common to all major histocompatibility complex class II gene promoters. Our data show that the IL-4 promoter Y box -114CTGATTGG-107 significantly enhances overall promoter activity, since point mutations within this element diminish promoter activity by 85%. The factor binding this region is indistinguishable from the cloned nuclear factor NF-Y, as judged from interactions with specific anti-NF-Y monoclonal and polyclonal antibodies. Last, we point out the presence of two sites that share sequence identity to the OAP region of the ARRE-1 site within the IL-2 promoter (K. S. Ullman, W. M. Flanagan, C. A. Edwards, and G. R. Crabtree, Science 254:558-562, 1991). These regions, -85GTGTAATA-78 and -245GTGTAATT-238, reside adjacent to the NF(P) binding sites P1 and P4 and bind a distinct nuclear factor.

scholarly journals SHP-2 activates signaling of the nuclear factor of activated T cells to promote skeletal muscle growth

2006 ◽  
Vol 175 (1) ◽  
pp. 87-97 ◽  
Author(s):  
Mara Fornaro ◽  
Peter M. Burch ◽  
Wentian Yang ◽  
Lei Zhang ◽  
Claire E. Hamilton ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
T Cells ◽  
Intracellular Signaling ◽  
Tyrosine Phosphatase ◽  
Muscle Growth ◽  
Interleukin 4 ◽  
Type I ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Skeletal Muscle Growth

The formation of multinucleated myofibers is essential for the growth of skeletal muscle. The nuclear factor of activated T cells (NFAT) promotes skeletal muscle growth. How NFAT responds to changes in extracellular cues to regulate skeletal muscle growth remains to be fully defined. In this study, we demonstrate that mice containing a skeletal muscle–specific deletion of the tyrosine phosphatase SHP-2 (muscle creatine kinase [MCK]–SHP-2 null) exhibited a reduction in both myofiber size and type I slow myofiber number. We found that interleukin-4, an NFAT-regulated cytokine known to stimulate myofiber growth, was reduced in its expression in skeletal muscles of MCK–SHP-2–null mice. When SHP-2 was deleted during the differentiation of primary myoblasts, NFAT transcriptional activity and myotube multinucleation were impaired. Finally, SHP-2 coupled myotube multinucleation to an integrin-dependent pathway and activated NFAT by stimulating c-Src. Thus, SHP-2 transduces extracellular matrix stimuli to intracellular signaling pathways to promote skeletal muscle growth.

scholarly journals A potential role for nuclear factor of activated T-cells in receptor tyrosine kinase and G-protein-coupled receptor agonist-induced cell proliferation

2002 ◽  
Vol 368 (1) ◽  
pp. 183-190 ◽  
Author(s):  
Chandrahasa R. YELLATURU ◽  
Salil K. GHOSH ◽  
R.K. RAO ◽  
Lisa K. JENNINGS ◽  
Aviv HASSID ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Dna Synthesis ◽  
G Protein ◽  
Receptor Tyrosine Kinase ◽  
Binding Activity ◽  
Nuclear Factor ◽  
Activated T Cells ◽  
Dna Binding Activity ◽  
G Protein Coupled

We have studied the role of nuclear factor of activated T-cells (NFAT) transcription factors in the induction of vascular smooth muscle cell (VSMC) growth by platelet-derived growth factor-BB (PDGF-BB) and thrombin, the receptor tyrosine kinase (RTK) and G-protein-coupled receptor (GPCR) agonists, respectively. NFATc1 but not NFATc2 or NFATc3 was translocated from the cytoplasm to the nucleus upon treatment of VSMCs with PDGF-BB or thrombin. Translocation of NFATc1 was followed by an increase in NFAT—DNA binding activity and NFAT-dependent reporter gene expression. Cyclosporin A (CsA), a potent and specific inhibitor of calcineurin, a calcium/calmodulin-dependent serine phosphatase involved in the dephosphorylation and activation of NFATs, blocked NFAT—DNA binding activity and NFAT-dependent reporter gene expression induced by PDGF-BB and thrombin. CsA also completely inhibited PDGF-BB- and thrombin-induced VSMC growth, as measured by DNA synthesis and cell number. In addition, forced expression of the NFAT-competing peptide VIVIT for calcineurin binding significantly attenuated the DNA synthesis induced by PDGF-BB and thrombin in VSMCs. Together, these findings for the first time demonstrate a role for NFATs in RTK and GPCR agonist-induced growth in VSMCs.

scholarly journals Vascular Endothelial Growth Factor Activates Nuclear Factor of Activated T Cells in Human Endothelial Cells: a Role for Tissue Factor Gene Expression

1999 ◽  
Vol 19 (3) ◽  
pp. 2032-2043 ◽  
Author(s):  
Angel Luis Armesilla ◽  
Elisa Lorenzo ◽  
Pablo Gómez del Arco ◽  
Sara Martínez-Martínez ◽  
Arantzazu Alfranca ◽  
...  
Keyword(s):  
Gene Expression ◽  
Vascular Endothelial Growth Factor ◽  
T Cells ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Nuclear Factor ◽  
Promoter Activation ◽  
Activated T Cells ◽  
Endothelial Growth Factor

ABSTRACT Vascular endothelial growth factor (VEGF) is a potent angiogenic inducer that stimulates the expression of tissue factor (TF), the major cellular initiator of blood coagulation. Here we show that signaling triggered by VEGF induced DNA-binding and transcriptional activities of nuclear factor of activated T cells (NFAT) and AP-1 in human umbilical vein endothelial cells (HUVECs). VEGF also induced TF mRNA expression and gene promoter activation by a cyclosporin A (CsA)-sensitive mechanism. As in lymphoid cells, NFAT was dephosphorylated and translocated to the nucleus upon activation of HUVECs, and these processes were blocked by CsA. NFAT was involved in the VEGF-mediated TF promoter activation as evidenced by cotransfection experiments with a dominant negative version of NFAT and site-directed mutagenesis of a newly identified NFAT site within the TF promoter that overlaps with a previously identified κB-like site. Strikingly, this site bound exclusively NFAT not only from nuclear extracts of HUVECs activated by VEGF, a stimulus that failed to induce NF-κB-binding activity, but also from extracts of cells activated with phorbol esters and calcium ionophore, a combination of stimuli that triggered the simultaneous activation of NFAT and NF-κB. These results implicate NFAT in the regulation of endothelial genes by physiological means and shed light on the mechanisms that switch on the gene expression program induced by VEGF and those regulating TF gene expression.

scholarly journals Nuclear Factor of Activated T Cells and Cytokines Gene Expression of the T Cells in AIDS Patients with Immune Reconstitution Inflammatory Syndrome during Highly Active Antiretroviral Therapy

2017 ◽  
Vol 2017 ◽  
pp. 1-7 ◽  
Author(s):  
Jia Sun ◽  
Heling Chen ◽  
Yirui Xie ◽  
Junwei Su ◽  
Ying Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Immune Reconstitution Inflammatory Syndrome ◽  
Highly Active Antiretroviral Therapy ◽  
Immune Reconstitution ◽  
High Expression ◽  
Nuclear Factor ◽  
Aids Patients ◽  
Activated T Cells ◽  
Inflammatory Syndrome

Background. The etiology of immune reconstitution inflammatory syndrome (IRIS) in AIDS patients after the initiation of HAART remains unknown. Several researches indicated that the development of IRIS is associated with the production and variation of cytokines, whose gene expression are closely related to the Ca2+/CN-nuclear factor of activated T cells (NFAT) pathway.Methods. We studied the expression of NFAT isoforms and their major target cytokines genes in peripheral blood CD3+T cells of subjects through fluorescence quantitative PCR and explored the expression changes of these genes before and after HAART.Results. After the initiation of HARRT, NFAT1, IL-6, and IL-8 gene expression showed a reversal trend in the CD3+T cells of the IRIS group and changed from low expression before HARRT to high expression after HARRT. In particular, the relative gene expression of NFAT1 was markedly higher compared with the other three isoforms. The IRIS group also showed higher NFAT4, NFAT2, NFAT1, IL-1β, IL-10, IL-2, IL-18, and TNF-αgene expression than the non-IRIS group.Conclusion. This study suggested that high expression levels of IL-2, IL-6, IL-8, TNF-α, IL-1β, IL-10, IL-12, and IL-18 can predict the risk of IRIS. The increased expression of NFAT1 and NFAT4 may promote the expression of cytokines, such as IL-6, IL-8, and TNF-α, which may promote the occurrence of IRIS.

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