scholarly journals Band-pass processing in a GPCR signaling pathway selects for NFAT transcription factor activation

2015 ◽  
Vol 7 (11) ◽  
pp. 1378-1386 ◽  
Author(s):  
M. Sumit ◽  
R. R. Neubig ◽  
S. Takayama ◽  
J. J. Linderman
Keyword(s):  
Transcription Factor ◽  
Signaling Pathway ◽  
Gpcr Signaling ◽  
Transcription Factor Activation ◽  
Nfat Transcription Factor ◽  
Band Pass ◽  
Kinetics Of ◽  
Signal Activation ◽  
Stimulation Of

Pulsatile stimulation of a GPCR pathway reveals that the downstream signal activation is optimized for intermediate frequencies in a band-pass manner that can be explained by the kinetics of the signaling pathway.

scholarly journals Tyrosine-Phosphorylation-Dependent Translocation of the SLAT Protein to the Immunological Synapse Is Required for NFAT Transcription Factor Activation

Immunity ◽  
2008 ◽  
Vol 29 (5) ◽  
pp. 704-719 ◽  
Author(s):  
Stéphane Bécart ◽  
Ann J. Canonigo Balancio ◽  
Céline Charvet ◽  
Sonia Feau ◽  
Caitlin E. Sedwick ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Tyrosine Phosphorylation ◽  
Immunological Synapse ◽  
Transcription Factor Activation ◽  
Nfat Transcription Factor

scholarly journals The Antiapoptotic Gene mcl-1 Is Up-Regulated by the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway through a Transcription Factor Complex Containing CREB

1999 ◽  
Vol 19 (9) ◽  
pp. 6195-6206 ◽  
Author(s):  
Ju-Ming Wang ◽  
Jyh-Rong Chao ◽  
Wannhsin Chen ◽  
Min-Liang Kuo ◽  
Jeffrey J.-Y. Yen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Signaling Pathway ◽  
Reporter Gene ◽  
Akt Signaling ◽  
Binding Activity ◽  
Akt Signaling Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Transcription Factor Complex ◽  
Stimulation Of

ABSTRACT mcl-1 is an immediate-early gene activated by the granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin 3 (IL-3) signaling pathways and plays an important role in the viability response of these cytokines. In this study, we demonstrated that cytokine stimulation of mcl-1 mRNA and protein expression were attenuated by pretreatment of cells with phosphatidylinositol 3-kinase (PI3-K) inhibitors. Reporter gene assays further showed that the PI3-K/Akt signaling pathway was involved in IL-3 activation of mcl-1 gene transcription. Analysis of the mcl-1 promoter revealed that both promoter elements, SIE at position −87 and CRE-2 at −70, contribute to IL-3 stimulation of mcl-1 gene expression. Although either the SIE site or the CRE-2 site alone was sufficient to confer IL-3 inducibility on a heterologous promoter, only IL-3 activation of the CRE-2 reporter was mediated via the PI3-K/Akt pathway. The SIE binding activity was constitutively high in cells deprived of or stimulated by IL-3. In contrast, the CRE-2 binding activity was low in cytokine-starved cells and was strongly induced within 1 h following cytokine treatment of cells. In addition, cytokine induction of the CRE-2 but not of the SIE binding activity was dependent on activation of the PI3-K/Akt signaling pathway. Lastly, we showed that CREB was one component of the CRE-2 binding complex and played a role in IL-3 activation of themcl-1 reporter gene. Taken together, our results suggest that both PI3-K/Akt-dependent and -independent pathways contribute to the IL-3 activation of mcl-1 gene expression. Activation ofmcl-1 by the PI3-K/Akt-dependent pathway is through a transcription factor complex containing CREB.

Transcription factor activation and functional stimulation of human monocytes

1992 ◽  
Vol 16 (1) ◽  
pp. 37-45 ◽  
Author(s):  
B KAMINSKA ◽  
L KACZMAREK ◽  
L MALAGUARNERA ◽  
A ARCIDIACONO ◽  
L MESSINA ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Human Monocytes ◽  
Transcription Factor Activation ◽  
Functional Stimulation ◽  
Stimulation Of

scholarly journals Stimulation of the Proliferation of Mouse and Human Definitive Erythroid Progenitors By Activation of the Vitamin D Receptor Transcription Factor

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1029-1029
Author(s):  
Margaret H. Baron ◽  
Jeffrey H. Barminko ◽  
Brad M. Reinholt ◽  
Mohandas Narla
Keyword(s):  
Vitamin D ◽  
Transcription Factor ◽  
Signaling Pathway ◽  
Vitamin D Receptor ◽  
Vitamin D3 ◽  
Fetal Liver ◽  
Nuclear Hormone Receptor ◽  
Erythroid Progenitors ◽  
Erythroid Progenitor ◽  
Stimulation Of

Abstract How the proliferation of erythroid progenitors is regulated is still now well understood. We found, using a computational analysis, that the vitamin D receptor(Vdr) nuclear hormone receptor transcription factor gene is expressed in the fetal and adult (definitive) but not the embryonic (primitive) stage of mouse erythroid ontogeny. Vdr is transcribed in definitive erythroid (EryD) progenitors and was downregulated during their maturation. VDR transcription factor activation by its ligand vitamin D3 (1,25(OH)2D3) results in conformational changes that stabilize the protein and induce its translocation into the nucleus, where it recruits co-regulatory complexes. The VDR signaling pathway has been studied primarily in the biology of bone but has been largely unexplored in erythropoiesis, where the limited published studies were performed almost exclusively in leukemic cell lines and not in normal primary cells. Activation of Vdr signaling by the vitamin D3 agonist calcitriol increased the outgrowth of EryD colonies from fetal liver and adult bone marrow, maintained progenitor potential, and delayed terminal erythroid maturation, as revealed by clonogenic assays, suspension culture studies, cell surface phenotype, and gene expression analyses. The stimulation in growth of erythroid progenitors resulted in a large increase in the numbers of mature red blood cells. The early (cKit+CD71lo/neg) but not the late (cKit+CD71hi) EryD progenitor subset of Linneg cKit+ cells was responsive both to calcitriol and to calcipotriol (which is 1-to-200 fold less potent in its calcemic effects than calcitriol). Therefore, the increase in progenitor numbers in response to calcitriol is mediated through activation of VDR rather than by effects on calcium flux. In preliminary studies of human Lineageneg cells, we find that the vitamin D agonists calcitriol and calcipotriol increase the numbers of CFU-E colony numbers from peripheral blood or BM. These results are similar to our findings for mouse. The glucocorticoid receptor (Gr), like Vdr, is a member of the nuclear hormone receptor transcription factor family and has been shown to stimulate the proliferation of cKit+CD71lo/neg cells. To determine whether the Vdr and Gr signaling pathways can cooperate to modulate erythroid progenitor growth, cKit+CD71lo/negcells were cultured with or without calcitriol, dexamethasone, or the two ligands in combination. Culture of cKit+CD71lo/neg progenitors in the presence of both calcitriol and dexamethasone resulted in an increase in proliferation that was at least additive, compared to either ligand alone, suggesting a role in stress erythropoiesis. This possibility is supported by our recent finding that an erythroid specific deletion in Vdr that interferes with DNA binding results in a reticulocytosis that occurs earlier and is more pronounced than in control animals, in response to phenylhydrazine (PHZ)-induced anemia. In addition, this deletion in Vdr blocked the increase in early erythroid progenitors from fetal liver seen for wild type mice. Lentivirus shRNA-mediated knockdown of Vdr expression abrogated the stimulation of early erythroid progenitor growth by calcitriol. These findings suggest that Vdr has a cell-intrinsic function in early erythroid progenitors. Activation of Vdr by calcitriol blocked the up regulation of the erythroid transcription factor genes Gata1, Fog1 and Klf1. In contrast, expression of genes known to regulate erythroid progenitors (Gata2, Zfp36l2, Bmi1, and Hopx) was not affected by Vdr signaling. Therefore, other genes must be involved in the Vdr signaling pathway in erythroid progenitors. Targeting of downstream components of the VDR signaling pathway could lead to new approaches for expansion of erythroid progenitors ex vivo. (This work was supported by grants to MHB from the NIH, R01 DK102945 and HL62248.) Disclosures No relevant conflicts of interest to declare.

Chemotaxis and Transcription Factor Activation of Wild-Type and CCR6-Transfected RLE-6TN

Pneumologie ◽  
2012 ◽  
Vol 66 (11) ◽  
Author(s):  
K Hoehne ◽  
H Eibel ◽  
M Grimm ◽  
M Idzko ◽  
J Müller-Quernheim ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Wild Type ◽  
Transcription Factor Activation

scholarly journals Antigen-driven EGR2 expression is required for exhausted CD8+ T cell stability and maintenance

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Mayura V. Wagle ◽  
Stephin J. Vervoort ◽  
Madison J. Kelly ◽  
Willem Van Der Byl ◽  
Timothy J. Peters ◽  
...  
Keyword(s):  
T Cells ◽  
Transcription Factor ◽  
Cd8 T Cell ◽  
Chronic Stimulation ◽  
Epigenetic State ◽  
Multiple Differentiation ◽  
Cell Stability ◽  
Substantial Interest ◽  
Transcriptional State ◽  
Stimulation Of

AbstractChronic stimulation of CD8+ T cells triggers exhaustion, a distinct differentiation state with diminished effector function. Exhausted cells exist in multiple differentiation states, from stem-like progenitors that are the key mediators of the response to checkpoint blockade, through to terminally exhausted cells. Due to its clinical relevance, there is substantial interest in defining the pathways that control differentiation and maintenance of these subsets. Here, we show that chronic antigen induces the anergy-associated transcription factor EGR2 selectively within progenitor exhausted cells in both chronic LCMV and tumours. EGR2 enables terminal exhaustion and stabilizes the exhausted transcriptional state by both direct EGR2-dependent control of key exhaustion-associated genes, and indirect maintenance of the exhausted epigenetic state. We show that EGR2 is a regulator of exhaustion that epigenetically and transcriptionally maintains the differentiation competency of progenitor exhausted cells.

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