Instead, we identify the FGF-stimulated CREB kinase as MAP kinase-activated protein (MAPKAP) kinase-2, an enzyme that lies immediately downstream of p38 MAP kinase, in a pathway that is also stimulated by cellular stresses. (dundee.ac.uk)
We show that MAPKAP kinase-2 phosphorylates CREB at Ser133 in vitro, that the FGF- or stress-induced activation of MAPKAP kinase-2 and phosphorylation of CREB and ATF-1 are prevented by similar concentrations of the specific p38 MAP kinase inhibitor SB 203580, and that MAPKAP kinase-2 is the only detectable SB 203580-sensitive CREB kinase in SK-N-MC cell extracts. (dundee.ac.uk)
We as well as others have shown that two transcription factors activating transcription factor-1 (ATF-1)2 and cAMP-response element-binding protein (CREB) are activated and overexpressed Helicid in melanoma during its progression toward the malignant phenotype (9-13). (antiviralbiologic.com)
Stimuli such as growth factors neurotransmitters inflammatory biolipids stress signals or other factors that elevate intracellular cAMP or Ca2+ levels can activate CREB/ATF-1 through phosphorylation at Ser133 by protein kinase A or mitogen-activated protein kinases (MAPK) (14-17). (antiviralbiologic.com)
second CREB and ATF-1 act as survival factors for human melanoma cells. (antiviralbiologic.com)
Recently we have exhibited that phosphorylation of CREB and ATF-1 can be stimulated by a bioactive lipid platelet-activating factor (PAF) in metastatic melanoma cells (17). (antiviralbiologic.com)
The transcription factor ATF-2 (also called CRE-BP1) binds to both AP-1 and CRE DNA response elements and is a member of the ATF/CREB family of leucine zipper proteins. (thermofisher.com)
ATF2 is a member of the ATF/CREB family of basic region leucine zipper DNA binding proteins that regulates transcription by binding to a consensus cAMP response element (CRE) in the promoter of various viral and cellular genes. (ningbobio.com)
ATF2 is a nuclear protein that binds DNA as a dimer and can form dimers with members of the ATF/CREB and Jun/Fos families. (ningbobio.com)
Small heterodimer partner-interacting leucine zipper (SMILE) is a member of the cAMP response element-binding protein / activator transcription factor (CREB/ATF) family of basic leucine zipper (bZIP) transcription factors. (etals.org)
Kinase12
GS-002 also induced endoplasmic reticular (ER) stress as evidenced by increases in ER stress-responsive proteins including glucose-regulated protein 78 (GRP78), growth arrest- and DNA damage-inducible gene 153 (GADD153), phosphorylated eukaryotic initiation factor 2 α (eIF2 α ), phosphorylated protein endoplasmic-reticular-resident kinase (PERK), and ATF-3. (hindawi.com)
The induction of ATF-3 expression was mediated by mitogen-activated protein kinase (MAPK) signaling pathways in GS-002-treated cells. (hindawi.com)
Previous studies reported that ATF-3 was induced by treating cells with antitumorigenic compounds [ 14 - 18 ] and a phosphoinositide 3-kinase inhibitor [ 19 ]. (hindawi.com)
These findings provide new molecular basis for further understanding the mechanisms involved in ATP functions, as a signal transducer and activator of MAP kinase cascades, in Caco-2 cells derived from human colon adenocarcinoma. (conicet.gov.ar)
inositol-requiring enzyme 1 (IRE1α), PRKR-like ER kinase (PERK) and activating transcription factor-6 (ATF-6). (spandidos-publications.com)
The General Control Nonderepressible 2 (GCN2) kinase is a conserved member of the integrated stress response (ISR) pathway that represses protein translation and helps cells to adapt to conditions of nutrient shortage. (biomedcentral.com)
In the retina overexpression of VEGF reduces phosphorylation of p38 MAP kinase a stress-activated enzyme that can initiate apoptosis in neurons (Hou 2006b). (bioinf.org)
Data are normalized … Experiments to determine the activity of phophorylated p38 MAP kinase were performed using the ATF-2 fusion protein as a substrate and its level detected by western blot analysis. (bioinf.org)
Dissociation of VEGF effects on p38 MAP kinase activity and on neuronal survival We examined the ability of VEGF to affect p38 MAP kinase activity as indicated by ATF-2 phosphorylation (Fig. 3A) and neuronal survival (Fig. 3B) in the presence of a p38 MAP kinase inhibitor (SB203580) or the p38 MAP kinase activator anisomycin. (bioinf.org)
Activation of cyclin D1 by estradiol and spermine in MCF-7 breast cancer cells: a mechanism involving the p38 MAP kinase and phosphorylation of ATF-2. (jefferson.edu)
ATF-2 interacts with a variety of viral oncoproteins and cellular tumor suppressors and is a target of the SAPK/JNK and p38 MAP kinase signaling pathways. (thermofisher.com)
ATF-2 is normally activated in response to signals that converge on stress-activated protein kinases p38 and JNK. (wikipedia.org)
8000 Bahía Blanca, Argentina In the present work, we examined the role of ATP in the activation of the MAP kinases (MAPKs) ERK1/2, JNK1/2 and p38 and their involvement in the modulation of transcription factors and proliferation of human colon cancer Caco-2 cells. (conicet.gov.ar)
In addition, western blot analysis revealed that ATP-induced phosphorylation of MAPKs in Caco-2 cells was dependent on calcium influx and intracellular calcium release, Src-family tyrosine kinases, and partially dependent on the cAMP/PKA and PKC pathways. (conicet.gov.ar)
In most metazoans, GCN2 is one of the four known kinases that phosphorylate eukaryotic initiation factor 2, α subunit (eIF2α) to inhibit translation initiation [ 19 ]. (biomedcentral.com)
Recruitment of additional factors, including kinases, leads to phosphorylation of LRP6. (nature.com)
Distinct cellular stresses cause the phosphorylation and activation the eIF2α kinases PERK, PKR, GCN2 and HRI. (biomedcentral.com)
Flow chart of the FACE In-Cell Western method that uses a cell-based ELISA to measure the levels of the native and phospho forms of signaling proteins and kinases that are activated by phosphorylation. (activemotif.com)
The epidermal growth factor receptor (EGFR) specific inhibitor AG1478 decreased ERK1/2, JNK1/2 and p38 MAPK phosphorylation by ATP, suggesting that EGFR transactivation is important for ATP-mediated stimulation of MAPKs in this intestinal cell line. (conicet.gov.ar)
Moreover, MAPKs participate in the induction and phosphorylation of the dual phosphatase MKP-1, which is known to inactivate ERK, JNK and p38 MAPK by dephosphorylating two critical sites in the activation loop. (conicet.gov.ar)
SB203580 (4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-5-(4-pyridyl)-imidazole) is a selective inhibitor of p38 MAPK. (antibodyguide.com)
Both SAPK and p38 MAPK have been shown to phosphorylate ATF-2 at these sites in vitro and in cells transfected with ATF-2. (thermofisher.com)
Leucine zipper1
Small heterodimer partner(SHP)-interacting leucine zipper protein(SMILE)은 처음에 Zhangfei라고 불리는 basic leucin zipper protein(bZIP) 전사조절인자로, 바이러스 단백질 VP16을 통해 단순포진바이러스(Herpes simplex virus, HSV)의 극초기 유전자(immediate early genes) 전이 활성화를 위해 필요한 수용체 세포 인자(host cell factor, HCF)에 결합하는 보조조절인자(coregulator) 중 하나로 알려졌다[ 1 , 2 ]. (etals.org)
Activating transcription factor 2, also known as ATF2, is a protein that, in humans, is encoded by the ATF2 gene. (wikipedia.org)
Activating transcription factor-(ATF-) 3, a stress-inducible transcription factor, is rapidly upregulated under various stress conditions and plays an important role in inducing cancer cell apoptosis. (hindawi.com)
The genetic model of DR - the eat-2 mutant - has a decreased pumping rate, thus ingesting less bacteria, and requires the FoxA transcription factor PHA-4 [ 8 ] and the dimethoxy ubiquinone hydroxylase CLK-1 [ 9 ] to extend its lifespan. (biomedcentral.com)
Western blot was performed using Anti-ATF2 Recombinant Rabbit Monoclonal Antibody (SZ17-01) (Product # MA5-32022) and 60kDa and 40kDa bands corresponding to Cyclic AMP-dependent transcription factor ATF-2 was observed across all the tested cell lines and tissues, except Mouse Skeletal Muscle. (thermofisher.com)
ATF21
Western blot analysis of ATF2 phosphorylation expression in MDA-MB-435 whole cell lysates,The lane on the left is treated with the antigen-specific peptide. (zfdows.com)
Overexpression1
Metastasis-associated protein 2 is a repressor of estrogen receptor alpha whose overexpression leads to estrogen-independent growth of human breast cancer cells. (jefferson.edu)
We demonstrate, by confocal microscopy, that stimulation of Caco-2 cells with ATP results in the translocation of active MAPKs to the nucleous where they induce the expression of c-Fos and Jun family proteins, the phosphorylation of ATF-1, ATF-2 and JunD transcription factors and stimulate Caco-2 cell proliferation. (conicet.gov.ar)
[11] The N- and C- terminal of the histone proteins are post-translationally modified by the removal or addition of acetyl (acetylation), phosphate (phosphorylation), methyl (methylation), ubiquitin (ubiquitination), and ubiquitin-like modifier (SUMOylating) groups. (cloudfront.net)
The resident transmembrane proteins (PERK, ATF6, and IRE1) are the three ER sensors involved in unfolded protein response (UPR), which functions to maintain the homeostasis of ER by attenuating protein translation, reducing the load of newly synthesized protein, degrading misfolded or unfolded protein, and upregulating chaperones, such as Grp78 [ 2 ]. (hindawi.com)
To assay the expression level of a protein, or the phosphorylation state of a signaling protein, Western blots are often employed, with phospho-specific antibodies used to specifically detect the phosphorylated states of the proteins in question. (activemotif.com)
Apoptosis7
Furthermore, we found that GS-002 induced more cell apoptosis in ATF-3-overexpressing cells. (hindawi.com)
These results suggest that the induction of apoptosis by the propolis derivative, GS-002, is partially mediated through ER stress and ATF-3-dependent pathways, and GS-002 has the potential for development as an antitumor drug. (hindawi.com)
New anticancer therapy strategies refer to the inhibition of CDK-cyclin complexes as an important target to prevent uncontrolled proliferation and induce apoptosis in cancer cells ( 2 ). (spandidos-publications.com)
In an analogous manner intracellular expression of an inhibitory anti-ATF-1 single chain variable fragment (ScFv) antibody in MeWo melanoma cells suppresses their tumorigenicity and metastatic potential in nude mice (21 22 Expression of ScFv anti-ATF-1 renders the melanoma cells susceptible to thapsigargin-induced apoptosis and causes massive apoptosis in tumors transplanted subcutaneously into nude mice (23). (antiviralbiologic.com)
Whether 5,7,3′,4′-tetramethoxyflavone (TMF) plays the chondroprotective role in inhibition of PGE 2 -induced chondrocytes apoptosis associating with ERS has not been reported. (hindawi.com)
By treatment with PGE 2 , the chondrocytes apoptosis was significantly increased, the proapoptotic CHOP and JNK were upregulated, the prosurvival GRP78 and XBP1 were downregulated, and GSK-3 β was also upregulated. (hindawi.com)
Finally, the inflammatory cytokine PGE 2 can activate ERS signaling and promote chondrocytes apoptosis, which might be associated with upregulation of GSK-3 β . (hindawi.com)
Induces2
ATF-3 induces DNA synthesis and expression of cyclin D1 in hepatocytes [ 21 ] and is involved in serum-induced cell proliferation as a target gene of c-myc [ 10 ]. (hindawi.com)
Our results showed that ATP induces the phosphorylation of MAPKs in a time and dose-dependent manner, peaking at 5 min at 10 M ATP. (conicet.gov.ar)
PERK3
HCT 116 colon cancer cells were exposed to purvalanol, which activated ER stress via upregulation of PERK, IRE1α gene expression, eIF-2α phosphorylation and ATF-6 cleavage at early time-points in the HCT 116 colon cancer cells. (spandidos-publications.com)
To investigate this, the activation of PERK, ATF6, and IRE1 signaling pathways in ERS in chondrocytes pretreated with PGE 2 was studied. (hindawi.com)
PERK and ATF6 signaling pathways activate the downstream factor CHOP to downregulate the expression of Bcl-2, an antiapoptotic protein, and contribute to programmed cell death [ 5 ], which has been comprehensively reviewed [ 6 ]. (hindawi.com)
EIF22
Phosphorylation of eIF2α on Ser51 inhibits 5' cap-dependent mRNA translation, resulting in the global suppression of protein synthesis to facilitate adaptation to a variety of stresses linked to protein synthesis, including proteotoxic stress, viral replication, heme depletion and amino acid withdrawal [ 2 ]. (biomedcentral.com)
Paradoxically, eIF2α phosphorylation also results in the increased translation of select mRNA bearing upstream open reading frames that favor 5' cap-independent translation [ 3 ]. (biomedcentral.com)
Residues2
TGF-β1 is a 112 amino-acid homodimer with nine cysteine residues, Figure 1-2. (janechin.net)
They contain a short beta hairpin and an alpha helix (beta/beta/alpha structure), where a single zinc atom is held in place by Cys(2)His(2) (C2H2) residues in a tetrahedral array. (embl.de)
Pathways1
DR acts by promoting stress response pathways and preventing age-related functional decline, delaying the appearance of cardiovascular diseases, type 2 diabetes, and neurodegeneration in mammals, including non-human primates [ 6 ]. (biomedcentral.com)
Gene1
This leads to translation of an alternative and functional open reading frame of the ATF4 gene ( atf-5 in C. elegans ) [ 20 , 21 ]. (biomedcentral.com)
Stresses1
The integrated stress response (ISR) is an adaptive signaling pathway that contributes to the biology of a number of hematologic malignancies since they are inherently prone to numerous cellular stresses [ 2 ]. (biomedcentral.com)
Mammalian2
Several studies implicate abnormal activation of ATF-2 in growth and progression of mammalian skin tumors. (wikipedia.org)
Two cannabinoid receptors have been characterized and cloned from mammalian tissues: the "central" CB 1 receptor and the "peripheral" CB 2 receptor. (aacrjournals.org)
Cellular2
Various forms of cellular stress, including genotoxic agents, inflammatory cytokines and UV irradiation, stimulate the transcriptional activity of ATF-2. (thermofisher.com)
The ISR (Fig. 1 ) is a complex signaling pathway that regulates cellular responses to stress stimuli and enables either adaptation or the instigation of cell death mechanisms [ 2 ]. (biomedcentral.com)
Activation3
In breast cancer, ATF-3 enhances cancer cell-initiating features [ 22 ] and is associated with activation of the canonical Wnt/ β -catenin pathway [ 23 ]. (hindawi.com)
In this paper, we will discuss whether PGE 2 can induce activation of ERS and GSK-3 β in chondrocytes and the protection role of TMF. (hindawi.com)
핵수용체는 리간드 비의존적인 전사 활성 도메인(Activation Function 1, AF-1), DNA 결합 도메인(DNA binding domain), hinge 도메인, 리간드 결합 도메인(ligand binding domain, LBD), 리간드 의존적인 전사 활성 도메인(AF-2) 5개의 도메인으로 이루어져 있다. (etals.org)
Cells6
ATF-2 phosphorylation in response to treatment of cells with tumor promoter phorbol ester has been demonstrated. (wikipedia.org)
ATF-2 may mediate oncogenesis caused by mutant Ras protein and regulate maintenance of the aggressive cancer phenotype of some types of epithelial cells. (wikipedia.org)
On the other hand, ATF-3 is rapidly induced in cells treated with growth stimulators such as serum and growth factors [ 20 ]. (hindawi.com)
Cells were cultured at 37°C with 5% CO 2 in 10% FBS of the medium, including DMEM (low glucose), 100 U/mL penicillin, and 100 mg/mL streptomycin. (hindawi.com)
Open up in another windows Fig.?2 Cells react to SUV4-20 inhibition immediately and recover rapidly after removal of SUV4-20 inhibitor. (researchensemble.com)
Transforming growth factor-beta (TGFβ) was discovered more than thirty years ago as a secreted polypeptide from sarcoma virus-infected cells that promoted the soft agar independent growth of normal rat kidney (NRK) cells [ 1 ] [ 2 ] . (encyclopedia.pub)
ERK11
In our present examine, we observed the enhanced expression of PKCs (PKCa, PKCb and PKCe) and MAPKs (phospho- p38, phosphoJNK and phospho-ERK1/2) in STZ-induced diabetic kidney. (adenosine-kinase.com)
In our previous studies, we found that PGE 2 could upregulate the expression of GSK-3 β and this could be significantly inhibited by 5,7,3′,4′-tetramethoxyflavone (TMF), which is one of active polymethoxyflavone compounds isolated from Murraya exotica [ 9 ]. (hindawi.com)
The expression levels of TNF-α, IL-8, IL-12, MMP-2, and MMP-9 were detected using real-time PCR and ELISA. (aging-us.com)
Results: Firstly, the expression levels of TNF-α, IL-8, IL-12, MMP-2, MMP-9 and IL-1R1, as well as the ROS level, were significantly elevated by IL-1α but greatly suppressed by treatment with Apremilast. (aging-us.com)
Many classic mechanisms of chemoresistance have been widely researched from a genetic perspective, such as the abnormality of DNA damage repair (DDR) related genes, increased detoxification activity, the repressed chromatin state and drug efflux promoted by the high expression of multidrug resistance-associated protein 2 [ 5 ]. (ijbs.com)
MAPKs1
Moreover, UTP and ATPS but not ADP or ADPβS increased phosphorylation of MAPKs, indicating the involvement of, at least, P2Y2/P2Y4 purinergic receptor subtypes. (conicet.gov.ar)
Cell4
Purvalanol is a purine-derived CDKI that binds with a high selectivity and competitively to the ATP binding side of CDK1/2 and leads to G2/M cell cycle arrest ( 4 ). (spandidos-publications.com)
Comparative biochemical studies of rapamycin and wortmannin on transforming growth factor-beta 1 (TGF-beta1)-mediated G(1)-S cell cycle progression in C3H-10T1/2 embryonic fibroblasts. (janechin.net)
Fast Activated Cell-based ELISA (FACE™ In-Cell Western ) Kits provide a simple, sensitive method for detecting protein phosphorylation directly in the cell, without making extracts or performing electrophoresis and membrane blotting. (activemotif.com)
Mice2
Studies in mice indicate a role for ATF-2 in the development of nervous system and the skeleton. (wikipedia.org)
[2] In male mice, the epigenetic signal is maintained through the F1 generation. (cloudfront.net)
Stress1
Knockdown of the C. elegans IMPACT homolog impt-1 activated the ISR pathway and increased lifespan and stress resistance of worms in a gcn-2 -dependent manner. (biomedcentral.com)
Intracellular1
Significantly, the actions of both GLP-1 and forskolin were abolished by the selective Ca 2+ /calmodulin-dependent phosphatase 2B (calcineurin) inhibitor, FK506, as well as by the chelation of intracellular Ca 2+ by BAPTA (bis(2-aminophenoxy)ethane- N,N,N ′ ,N ′-tetraacetate). (diabetesjournals.org)
Signals1
[2] The signals that are maintained beyond the F2/F3 generation are referred to as transgenerational epigenetic inheritance (TEI), because initial environmental stimuli resulted in inheritance of epigenetic modifications. (cloudfront.net)
IMMUNE SYSTEM1
CB 2 receptors are almost exclusively found in the immune system, with the greatest density in the spleen ( 1 ). (aacrjournals.org)
Cancer2
Chemotherapy, including cisplatin (CDDP), remains a potent treatment for patients with late-stage liver cancer [ 2 , 3 ]. (ijbs.com)