scholarly journals Multiple Signaling Pathways Are Involved in the Interleukine-4 Regulated Expression of DC-SIGN in THP-1 Cell Line

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Changzhong Jin ◽  
Lijuan Wu ◽  
Jie Li ◽  
Meixin Fang ◽  
Linfang Cheng ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Site ◽  
Signaling Pathways ◽  
Specific Inhibitor ◽  
High Expression ◽  
Intercellular Adhesion Molecule ◽  
Erk Pathway ◽  
Regulated Expression ◽  
Multiple Signaling

Dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN) is an important pattern recognition receptor on dendritic cells (DCs), and its expression shows significant cytological and histological specificity, being interleukine-4 (IL-4) dependent. The signaling pathways through which IL-4 regulates expression of DC-SIGN are still unclear. We used phorbol 12-myristate 13-acetate- (PMA-) differentiated THP-1 cells as thein vitromodel of monocyte/macrophage cells to study the signaling pathways involved in IL-4-regulated expression of DC-SIGN. We found that a high expression of DC-SIGN could be induced by IL-4 at the levels of mRNA and cell surface protein. Upregulated expression of DC-SIGN was almost completely blocked by the specific inhibitor of ERK pathway, and partly reduced by the specific inhibitors of JAK-STAT and NF-κB pathways. The activation of the three signaling pathways was directly confirmed by testing the phosphorylation of protein kinase within the cytoplasm and nucleus over time. The analysis ofcis-acting elements of DC-SIGN promoter showed that the activity of DC-SIGN promoter without Ets-1 transcription factors binding site almost completely disappeared. Our results demonstrated that multiple signaling pathways are involved in IL-4 induced high expression of DC-SIGN on THP-1 cells, in which ERK pathway is the main signaling pathway and mediated by the Ets-1 transcription factors binding site.

A Serine Protease Activity Is Induced by G-CSF and Degrades Stat5 Proteins in Myeloid Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2180-2180
Author(s):  
Yaling Qiu ◽  
Dazhong Zhuang ◽  
Alexandra MacRae ◽  
Fan Dong
Keyword(s):  
Signaling Pathways ◽  
Protease Activity ◽  
Myeloid Cells ◽  
Granulocytic Differentiation ◽  
Protein Levels ◽  
Serine Protease Activity ◽  
Cell Type Specific ◽  
Multiple Signaling ◽  
Activation Status

Abstract Granulocytic progenitor cells become progressively less capable of proliferation and survival with terminal differentiation. Granulocyte colony-stimulating factor (G-CSF) is the major regulator of granulopoiesis and stimulates the activation of multiple signaling pathways including the signal transducer and activator of transcription 5 (Stat5) pathway. Little is known about the activation status of G-CSF-stimulated signaling pathways at the distinct stages of granulocytic differentiation. When myeloid 32D cells transfected with the G-CSF receptor were induced to differentiate with G-CSF, Stat5 activation in response to G-CSF was gradually attenuated. Activation of other signaling molecules including Stat1, Stat3, Erk1/2, JNK and p38 was not altered significantly. Stat5 activation was also downregulated in multipotent FDCP-mix cells, which differentiated into mature granulocytes upon induction with G-CSF, but not in pro-B BaF/3 transfected with the G-CSF receptor, which showed no terminal granulocytic differentiation in response to G-CSF, suggesting that the effect of G-CSF is cell type specific. Attenuated activation of Stat5 correlated with reduced Stat5 protein levels, which was associated with expression of a protease activity capable of degrading Stat5 protein in vitro. The Stat5 protease activity was upregulated when myeloid cells were induced to differentiate with G-CSF, but its upregulation by G-CSF was blocked upon expression of leukemogenic proteins Bcr-Abl and Tel-Jak2. The activity of the Stat5 protease was inhibited partially by PMSF and completely by a1-antitrypsin, suggesting that it belongs to the serine family of protease. Our data provide the first evidence that a Stat5 protease activity is upregulated by G-CSF and may have important implications for understanding the molecular mechanism by which G-CSF orchestrates granulopoiesis.

MAP kinases and the adaptive response to hypertonicity: functional preservation from yeast to mammals

2004 ◽  
Vol 287 (6) ◽  
pp. F1102-F1110 ◽  
Author(s):  
David Sheikh-Hamad ◽  
Michael C. Gustin
Keyword(s):  
Transcription Factors ◽  
Signaling Pathways ◽  
Adaptive Response ◽  
Mammalian Cells ◽  
Map Kinases ◽  
Current Knowledge ◽  
Cis Elements ◽  
P38 Kinase ◽  
Functional Preservation ◽  
Multiple Signaling

The adaptation to hypertonicity in mammalian cells is driven by multiple signaling pathways that include p38 kinase, Fyn, the catalytic subunit of PKA, ATM, and JNK2. In addition to the well-characterized tonicity enhancer (TonE)-TonE binding protein interaction, other transcription factors (and their respective cis elements) can potentially respond to hypertonicity. This review summarizes the current knowledge about the signaling pathways that regulate the adaptive response to osmotic stress and discusses new insights from yeast that could be relevant to the osmostress response in mammals.

scholarly journals Structural determinants of DNA recognition by plant MADS-domain transcription factors

2013 ◽  
Vol 42 (4) ◽  
pp. 2138-2146 ◽  
Author(s):  
Jose M. Muiño ◽  
Cezary Smaczniak ◽  
Gerco C. Angenent ◽  
Kerstin Kaufmann ◽  
Aalt D.J. van Dijk
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Binding Site ◽  
Structural Characteristics ◽  
Binding Specificity ◽  
Structural Motif ◽  
Dna Binding Specificity ◽  
Dna Binding Site ◽  
Carg Box

Abstract Plant MADS-domain transcription factors act as key regulators of many developmental processes. Despite the wealth of information that exists about these factors, the mechanisms by which they recognize their cognate DNA-binding site, called CArG-box (consensus CCW6GG), and how different MADS-domain proteins achieve DNA-binding specificity, are still largely unknown. We used information from in vivo ChIP-seq experiments, in vitro DNA-binding data and evolutionary conservation to address these important questions. We found that structural characteristics of the DNA play an important role in the DNA binding of plant MADS-domain proteins. The central region of the CArG-box largely resembles a structural motif called ‘A-tract’, which is characterized by a narrow minor groove and may assist bending of the DNA by MADS-domain proteins. Periodically spaced A-tracts outside the CArG-box suggest additional roles for this structure in the process of DNA binding of these transcription factors. Structural characteristics of the CArG-box not only play an important role in DNA-binding site recognition of MADS-domain proteins, but also partly explain differences in DNA-binding specificity of different members of this transcription factor family and their heteromeric complexes.

scholarly journals Multiple signaling pathways involved in stimulation of osteoblast differentiation by N-methyl-D-aspartate receptors activation in vitro

2011 ◽  
Vol 32 (7) ◽  
pp. 895-903 ◽  
Author(s):  
Jie-li Li ◽  
Lin Zhao ◽  
Bin Cui ◽  
Lian-fu Deng ◽  
Guang Ning ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Osteoblast Differentiation ◽  
Multiple Signaling ◽  
Stimulation Of

Abstract 403: BMPER Is an Angiogenic Modulator that is Regulated by KLF-15 and FoxO3A and Controls Bone Morphogentic Protein Activity

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Thomas Helbing ◽  
Jennifer Heinke ◽  
Franziska Volkmar ◽  
Leonie Wehofsits ◽  
Kim-Miriam Baar ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Binding Site ◽  
Luciferase Expression ◽  
Dependent Manner ◽  
Protein Activity ◽  
Angiogenic Activity ◽  
Bmp Pathway ◽  
Vasculogenesis And Angiogenesis

BMPER (bone morphogenetic protein [BMP] endothelial precursor cell derived regulator) is an extracellular protein, that interacts with BMPs and thereby modulates BMP dependent vasculogenesis and angiogenesis. Our previous observations suggest a complex regulation of BMPER expression. During embryogenesis BMPER is expressed at the time and at sites of vasculogenesis, whereas in the adult organism it is expressed in heart, lung and skin. Methods and Results: We have cloned the mouse BMPER promoter and appropriate deletion constructs into pGL3 to regulate luciferase expression. As predicted in silicio, we found that Sp1 and Sp1-like transcription factors such as the krueppel-like factors (KLFs) regulate BMPER transcription. KLF-15 resulted in a 4.5 fold upregulation. Accordingly, BMPER expression was inhibited by the Sp-1/SP-1 like inhibitor mitramycin A. Site specific mutation of a proximal KLF-15 binding site reduced the effect of KLF-15 on BMPER expression. Along the same lines, knock down of KLF-15 in HUVEC by siRNA reduced BMPER expression. The transactivating effect of KLF-15 could be competed away by coexpression of Sp-1 suggesting that both factors may compete for the same binding site in the BMPER promoter. In EMSA, an oligo representing a well characterized KLF-15 binding site in the AceCs2 promoter but not an oligo encoding for a NFkappa-B site competed with the oligo coding for the KLF-15 site in the BMPER promoter. In contrast FoxO3A, a member of the FoxO family of transcription factors, serves as an inhibitor of BMPER expression, as shown by gain and lack of FoxO3A experiments. Additionally, we found that BMPER stimulates angiogenesis in a BMP-4 dependent manner in several in vitro and in vivo assays. Vice versa, BMPER is necessary for BMP-4 to exert is angiogenic activity on endothelial cells. Conclusion: BMPER is upregulated by KLF-15 and inhibited by FoxO3a. BMPER has angiogenic activity and is a key modulator of the BMP pathway.

scholarly journals Colony-stimulating Factor-1 Receptor Utilizes Multiple Signaling Pathways to Induce Cyclin D2 Expression

2000 ◽  
Vol 11 (11) ◽  
pp. 3835-3848 ◽  
Author(s):  
Arunangsu Dey ◽  
Hongyun She ◽  
Leopold Kim ◽  
Allan Boruch ◽  
Deborah L. Guris ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Single Gene ◽  
Inhibitory Effect ◽  
Early Gene ◽  
Erk Pathway ◽  
Colony Stimulating Factor ◽  
Signaling Mechanism ◽  
Extracellular Signal ◽  
Multiple Signaling ◽  
Stimulating Factor

Colony-stimulating factor-1 (CSF-1) induces expression of immediate early gene, such as c-myc and c-fos and delayed early genes such as D-type cyclins (D1 and D2), whose products play essential roles in the G1 to S phase transition of the cell cycle. Little is known, however, about the cytoplasmic signal transduction pathways that connect the surface CSF-1 receptor to these genes in the nucleus. We have investigated the signaling mechanism of CSF-1-induced D2 expression. Analyses of CSF-1 receptor autophosphorylation mutants show that, although certain individual mutation has a partial inhibitory effect, only multiple combined mutations completely block induction of D2 in response to CSF-1. We report that at least three parallel pathways, the Src pathway, the MAPK/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway, and the c-myc pathway, are involved. Induction of D2 is partially inhibited in Src−/− bone marrow-derived macrophages and by Src inhibitor PP1 and is enhanced in v-Src-overexpressing cells. Activation of myc's transactivating activity selectively induces D2 but not D1. Blockade of c-myc expression partially blocks CSF-1-induced D2 expression. Complete inhibition of the MEK/ERK pathway causes 50% decrease of D2 expression. Finally, simultaneous inhibition of Src, MEK activation, and c-myc expression additively blocks CSF-1-induced D2 expression. This study indicates that multiple signaling pathways are involved in full induction of a single gene, and this finding may also apply broadly to other growth factor-inducible genes.

scholarly journals Effects of Axotomy on Cultured Sensory Neurons of Aplysia: Long-Term Injury-Induced Changes in Excitability and Morphology Are Mediated by Different Signaling Pathways

2008 ◽  
Vol 100 (6) ◽  
pp. 3209-3224 ◽  
Author(s):  
Supinder S. Bedi ◽  
Diancai Cai ◽  
David L. Glanzman
Keyword(s):  
Signaling Pathways ◽  
Sensory Neurons ◽  
Specific Inhibitor ◽  
Distinct Pattern ◽  
Extracellular Signal ◽  
Vitro Model ◽  
Induced Changes ◽  
And Control

To facilitate an understanding of injury-induced changes within the nervous system, we used a single-cell, in vitro model of axonal injury. Sensory neurons were individually dissociated from the CNS of Aplysia and placed into cell culture. The major neurite of some neurons was then transected (axotomized neurons). Axotomy in hemolymph-containing culture medium produced long-term hyperexcitability (LTH-E) and enhanced neuritic sprouting (long-term hypermorphogenesis [LTH-M]). Axotomy in the absence of hemolymph induced LTH-E, but not LTH-M. Hemolymph-derived growth factors may activate tyrosine receptor kinase (Trk) receptors in sensory neurons. To examine this possibility, we treated uninjured (control) and axotomized sensory neurons with K252a, an inhibitor of Trk receptor activity. K252a depressed the excitability of both axotomized and control neurons. K252a also produced a distinct pattern of arborizing outgrowth of neurites in both axotomized and control neurons. Protein kinase C (PKC) is an intracellular signal downstream of Trk; accordingly, we tested the effects of bisindolylmaleimide I (Bis-I), a specific inhibitor of PKC, on the axotomy-induced cellular changes. Bis-I blocked LTH-E, but did not disrupt LTH-M. Finally, because Trk activates the extracellular signal regulated kinase pathway in Aplysia sensory neurons, we examined whether this pathway mediates the injury-induced changes. Sensory neurons were axotomized in the presence of U0126, an inhibitor of mitogen-activated/extracellular receptor-regulated kinase. U0126 blocked the LTH-M due to axotomy, but did not impair LTH-E. Therefore distinct cellular signaling pathways mediate the induction of LTH-E and LTH-M in the sensory neurons.

Leukemic target susceptibility to natural killer cytotoxicity: relationship with BCR-ABL expression

Blood ◽  
2002 ◽  
Vol 99 (6) ◽  
pp. 2107-2113 ◽  
Author(s):  
Frédéric Baron ◽  
Ali G. Turhan ◽  
Julien Giron-Michel ◽  
Bruno Azzarone ◽  
Mohamed Bentires-Alj ◽  
...  
Keyword(s):  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Specific Inhibitor ◽  
Intercellular Adhesion Molecule ◽  
Target Cells ◽  
Intercellular Adhesion Molecule 1 ◽  
Down Regulation ◽  
Subsequent Decrease

Abstract Chronic myeloid leukemia is a clonal myeloproliferative expansion of transformed primitive hematopoietic progenitor cells characterized by high-level expression of BCR-ABL chimeric gene, which induces growth factor independence. However, the influence of BCR-ABL expression on cell-mediated cytotoxicity is poorly understood. In the present study, we asked whether BCR-ABL expression interferes with leukemic target sensitivity to natural killer (NK) cell cytolysis. Our approach was based on the use of 2 BCR-ABL transfectants of the pluripotent hematopoietic cell line UT-7 expressing low (UT-7/E8, UT-7/G6) and high (UT-7/9) levels of BCR-ABL. As effector cells, we used CD56bright, CD16−, CD2− NK cells differentiated in vitro from CD34 cord blood progenitors. We demonstrated that BCR-ABL transfectants UT-7/9 were lysed by NK cells with a higher efficiency than parental and low UT-7/E8.1 and UT-7/G6 transfectants. This enhanced susceptibility to lysis correlated with an increase in expression of intercellular adhesion molecule 1 (ICAM-1) by target cells. Treatment of UT-7/9 cells by STI571 (a specific inhibitor of the abl kinase) resulted in a decrease in NK susceptibility to lysis and ICAM-1 down-regulation in target cells. Furthermore, the constitutive activation of nuclear factor-κB (NF-κB) detected in BCR-ABL transfectant UT-7/9, was significantly attenuated when cells were treated by STI571. Interestingly, inhibition of NF-κB activation by BAY11-67082 (a specific NF-κB inhibitor) resulted in down-regulation of ICAM-1 expression and a subsequent decrease in NK-induced killing of UT-7/9 transfectants. Our results show that oncogenic transformation by BCR-ABL may increase susceptibility of leukemic progenitors to NK cell cytotoxicity by a mechanism involving overexpression of ICAM-1 as a consequence of NF-κB activation.

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