Search results for "Erk"
showing 10 items of 2599 documents
Induction of collagenase-3 (MMP-13) expression in human skin fibroblasts by three-dimensional collagen is mediated by p38 mitogen-activated protein k…
1999
Collagenase-3 (matrix metalloproteinase-13, MMP-13) is a recently identified human MMP with an exceptionally wide substrate specificity and restricted tissue-specific expression. Here we show that MMP-13 expression is induced in normal human skin fibroblasts cultured within three-dimensional collagen gel resulting in production and proteolytic activation of MMP-13. Induction of MMP-13 mRNAs by collagen gel was potently inhibited by blocking antibodies against alpha1 and alpha2 integrin subunits and augmented by activating antibody against beta1 integrin subunit, indicating that both alpha1 beta1 and alpha2 beta1 integrins mediate the MMP-13-inducing cellular signal generated by three-dimens…
Science Signaling Podcast: 5 August 2014
2014
This Podcast features an interview with Juliane Mooz and Krishnaraj Rajalingam, authors of a Research Article that appears in the 5 August 2014 issue of Science Signaling , about the cellular functions of the kinase ARAF. RAF proteins are serine-threonine kinases that mediate signaling through the mitogen-activated protein kinase (MAPK) pathway, and aberrant RAF activity can transform normal cells into cancerous cells. There are three RAFs in mammals: ARAF, BRAF, and CRAF. The most studied of these is BRAF, mutations in which are associated with various cancers. Whereas the cellular functions of BRAF and CRAF have been extensively studied, not much is known about ARAF. Mooz et al . found th…
The JAK2 Kinase Inhibitor LS104 Induces Growth-Arrest and Apoptosis in JAK2V617F Positive Cells.
2007
Abstract The JAK2V617F-mutation (V617F) is a novel, highly prevalent molecular marker in Ph-negative myeloproliferative disease (MPD). In vitro, the V617F mutation confers cytokine independent growth of Ba/F3 cells expressing erythropoietin receptor (EpoR) and constitutive activation of the JAK2 kinase and of the JAK-STAT pathway. In a murine bone-marrow transplant model the V617F-mutation alone is sufficient to induce a polycythemia vera-like phenotype. Therefore, mutant JAK2 kinase is a promising target for kinase inhibitor development. In this report, we characterize the small molecule LS104 (previously CR4; Grunberger et al., Blood 2003) as a novel non-ATP-competitive JAK2V617F kinase i…
Cigarette smoke increases Toll-like receptor 4 and modifies lipopolysaccharide-mediated responses in airway epithelial cells.
2008
Airway epithelium is emerging as a regulator of innate immune responses to a variety of insults including cigarette smoke. The main goal of this study was to explore the effects of cigarette smoke extracts (CSE) on Toll-like receptor (TLR) expression and activation in a human bronchial epithelial cell line (16-HBE). The CSE increased the expression of TLR4 and the lipopolysaccharide (LPS) binding, the nuclear factor-kappaB (NF-kappaB) activation, the release of interleukin-8 (IL-8) and the chemotactic activity toward neutrophils. It did not induce TLR2 expression or extracellular signal-regulated signal kinase 1/2 (ERK1/2) activation. The LPS increased the expression of TLR4 and induced bot…
The stimulation of arginine transport by TNFα in human endothelial cells depends on NF-κB activation
2004
In human saphenous vein endothelial cells (HSVECs), tumor necrosis factor-alpha (TNFalpha) and bacterial lipopolysaccharide (LPS), but neither interferon gamma (IFNgamma) nor interleukin 1beta (IL-1beta), stimulate arginine transport. The effects of TNFalpha and LPS are due solely to the enhancement of system y+ activity, whereas system y+L is substantially unaffected. TNFalpha causes an increased expression of SLC7A2/CAT-2B gene while SLC7A1/CAT-1 expression is not altered by the cytokine. The suppression of PKC-dependent transduction pathways, obtained with the inhibitor chelerytrhine, the inhibitor peptide of PKCzeta isoform, or chronic exposure to phorbol esters, does not prevent TNFalp…
Increased radioresistance via G12S K-Ras by compensatory upregulation of MAPK and PI3K pathways in epithelial cancer
2011
Background Irradiation-induced signaling via the 2 pathways, Raf-MEK-ERK and PI3K-Akt, is known to be closely associated with a limited response to radiotherapy. In the present study we analyzed the relevance of constitutively active K-Ras for postradiogenic pathway stimulation and the option of coordinated inhibition to overcome these rescue mechanisms. Methods We used 2 epithelial tumor cell lines as a model system, one of them harboring a G12S K-Ras mutation. Cells were irradiated and the effect of combined treatment with ionizing radiation and inhibitors on the expression of pERK and pAkt was determined by Western blotting. Additionally, clonogenic assays were performed to functionally …
Identification and characterization of an ABA-activated MAP kinase cascade in Arabidopsis thaliana.
2015
†These authors contributed equally to the work. Accession numbers Sequence data from this article can be found in Arabidopsis Genome Initiative or GenBank/EMBL databases under the following accession numbers: At1g10210 (MPK1), At1g59580 (MPK2), At2g43790 (MPK6), At2g18170 (MPK7), At1g18150 (MPK8), At4g36450 (MPK14), At5g40440 (MKK3), At2g32510 (MAP3K17) and At1g05100 (MAP3K18). SUMMARY Abscisic acid (ABA) is a major phytohormone involved in important stress-related and developmental plant processes. Recent phosphoproteomic analyses revealed a large set of ABA-triggered phosphoproteins as putative mitogen-activated protein kinase (MAPK) targets, although the evidence for MAPKs involved in AB…
Inhibition of c-MYC with involvement of ERK/JNK/MAPK and AKT pathways as a novel mechanism for shikonin and its derivatives in killing leukemia cells
2015
Leukemia remains life-threatening despite remarkable advances in chemotherapy. The poor prognosis and drug resistance are challenging treatment. Novel drugs are urgently needed. Shikonin, a natural naphthoquinone, has been previously shown by us to be particularly effective towards various leukemia cell lines compared to solid tumors. However, the underlying mechanisms are still poorly understood. Here, we investigated shikonin and 14 derivatives on U937 leukemia cells. Four derivatives (isobutyrylshikonin, 2-methylbutyrylshikonin, isovalerylshikonin and β,β-dimethylacrylshikonin) were more active than shikonin. AnnexinV-PI analysis revealed that shikonins induced apoptosis. Cell cycle G1/S…
p42 MAPK phosphorylates 80 kDa MARCKS at Ser-113.
1996
Abstract It is demonstrated here that p42 MAPKinase (p42 MAPK) phosphorylates the M yristoylated A lanine- R ich C - K inase S ubstrate (MARCKS) at Ser-113. In permeabilised Swiss 3T3 cells activation of protein kinase C (PKC) leads to p42 MAPK activation, but only the protein kinase C sites in MARCKS become phosphorylated and not Ser-113. The mitogen platelet-derived growth factor (PDGF) elicits the same response. These results demonstrate that while Ser-113 is a substrate for p42 MAPK in vitro and can be phosphorylated in vivo as shown by Taniguchi et al. [(1994) J. Biol. Chem. 269, 18299–18302], its phosphorylation is not subject to acute regulation by p42 MAPK in Swiss 3T3 cells.
Synthesis and biological evaluation of cycloalkylidene carboxylic acids as novel effectors of Ras/Raf interaction.
2002
The protooncogenes Ras and Raf play important roles in signal transduction pathways regulated by mitogen-activated protein kinases. Mutations of Ras that arrest the protein in its active state are frequently implicated in tumor formation. We used Ras and Raf proteins in the yeast two-hybrid system to search for natural or synthesized substances capable of modulating Ras/Raf interaction by specifically binding to one of the interacting partners. We found that cycloalkylidene carboxylic acids enhanced Ras/Raf interaction by acting on the cysteine-rich domain of Raf. Several analogues of the active substance 2-cyclohexylidene propanoic acid were synthesized and the importance of the semicyclic…