Search results for "Mitogen-Activated Protein Kinase"
showing 10 items of 353 documents
Ras-related GTPase Rhob represses NF-kappaB signaling.
2000
rhoB encoding a Ras-related GTPase is immediate-early inducible by genotoxic treatments, indicating that it is part of the cellular stress response. Here, we investigated the influence of RhoB on signal pathways that are rapidly evoked by genotoxic compounds. The data obtained show that wild-type RhoB neither affects activation of mitogen-activated protein kinases nor AP-1-dependent gene expression. However, RhoB inhibited both basal and genotoxic agent-stimulated activity of the transcription factor nuclear factor kappaB (NF-kappaB). Thus, RhoB attenuated alkylation-induced increase in the DNA binding activity of NF-kappaB and abrogated NF-kappaB-driven gene expression. Furthermore, RhoB i…
EphrinB2 controls vessel pruning through STAT1-JNK3 signalling
2014
Angiogenesis produces primitive vascular networks that need pruning to yield hierarchically organized and functional vessels. Despite the critical importance of vessel pruning to vessel patterning and function, the mechanisms regulating this process are not clear. Here we show that EphrinB2, a well-known player in angiogenesis, is an essential regulator of endothelial cell death and vessel pruning. This regulation depends upon phosphotyrosine-EphrinB2 signalling repressing c-jun N-terminal kinase 3 activity via STAT1. JNK3 activation causes endothelial cell death. In the absence of JNK3, hyaloid vessel physiological pruning is impaired, associated with abnormal persistence of hyaloid vessel…
Dissection of the elements of osmotic stress response transcription factor Hot1 involved in the interaction with MAPK Hog1 and in the activation of t…
2013
Abstract The response to hyperosmotic stress is mediated by the HOG pathway. The MAP kinase Hog1 activates several transcription factors, regulates chromatin-modifying enzymes and, through its interaction with RNA polymerase II, it directs this enzyme to osmotic stress-controlled genes. For such targeting, this kinase requires the interaction with transcription factors Hot1 and Sko1. However, phosphorylation of these proteins by Hog1 is not required for their functionality. In this study, we aim to identify the Hot1 elements involved in Hog1-binding and in the activation of transcription. Two-hybrid experiments demonstrated that the Hot1 sequence between amino acids 340 and 534 and the CD e…
The Saccharomyces cerevisiae Hot1p regulated gene YHR087W (HGI1) has a role in translation upon high glucose concentration stress.
2012
Abstract Background While growing in natural environments yeasts can be affected by osmotic stress provoked by high glucose concentrations. The response to this adverse condition requires the HOG pathway and involves transcriptional and posttranscriptional mechanisms initiated by the phosphorylation of this protein, its translocation to the nucleus and activation of transcription factors. One of the genes induced to respond to this injury is YHR087W. It encodes for a protein structurally similar to the N-terminal region of human SBDS whose expression is also induced under other forms of stress and whose deletion determines growth defects at high glucose concentrations. Results In this work …
MAP kinase p38 and its relation to T cell anergy and suppressor function of regulatory T cells
2008
Diverse regulatory T cell populations (Treg) are important for the control of self tolerance and immune homeostasis. These include naturally occurring CD4+CD25+ Treg (nTreg) and induced Treg (iTreg). Tolerogenic dendritic cells, modulated by IL-10, are able to convert peripheral T cells into iTreg. These are anergic and characterized by a G(1) cell cycle arrest, dependent on elevated levels of the cdk inhibitor p27(Kip1). Novel data revealed a distinct pattern of MAP kinase activation in iTreg different from clonal T cell anergy, with enhanced activation of the p38-MAPKAP-K2/3 pathway. p38 is involved in cell cycle control and its activity is a prerequisite for the induction and maintenance…
Heme oxygenase-1 inhibits apoptosis in Caco-2 cells via activation of Akt pathway
2005
Heme oxygenase-1 can play a protective role against cellular stress. In colon cancer cells, these effects would be relevant to oncogenesis and resistance to chemotherapy. The aim of the study was to examine the effects of heme oxygenase-1 induction on cell survival in a human colon cancer cell line, Caco-2. Serum deprivation induced apoptosis, reduced Akt and p38 phosphorylation, and increased p21(Cip/WAF1) levels. Heme oxygenase-1 induction by treatment with cobalt protoporphyrin IX resulted in resistance to apoptosis, activation of Akt, reduction in p21(Cip/WAF1) levels and modification of bcl2/bax ratio towards survival. Indomethacin reduced apoptosis but in contrast to heme oxygenase-1,…
Lovastatin causes sensitization of HeLa cells to ionizing radiation‐induced apoptosis by the abrogation of G2 blockage
2003
To investigate the effect of inhibition of Ras/Rho-regulated signalling by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) on radiation-induced cell killing and apoptosis.Different human cell lines were pretreated or not with lovastatin before exposure to gamma-rays. Afterwards, radiation-induced cell killing, formation and repair of double-strand breaks, activation of radiation-inducible signal mechanisms (i.e. p53, p21, extracellular-signal-related kinase (ERK), NF-kappaB), changes in cell cycle progression and apoptosis were analysed.As shown by a colony formation assay, lovastatin sensitized HeLa cells to gamma-radiation-induced cell killing. The lovastati…
Roflumilast N-oxide reverses corticosteroid resistance in neutrophils from patients with chronic obstructive pulmonary disease
2013
Background Glucocorticoid functions are markedly impaired in patients with chronic obstructive pulmonary disease (COPD). The phosphodiesterase 4 inhibitor roflumilast N-oxide (RNO) is the active metabolite of roflumilast approved as a treatment to reduce the risk of exacerbations in patients with severe COPD. Objective We sought to characterize the differential effects of RNO versus corticosteroids and their potential additive/synergistic effect in neutrophils from patients with COPD, thus providing scientific rationale for the combination of roflumilast with corticosteroids in the clinic. Methods Peripheral blood neutrophils were isolated from patients with COPD (n = 32), smokers (n = 7), …
“Cysteinyl leukotriene-1 receptor activation in a human bronchial epithelial cell line leads to signal transducer and activator of transcription 1-me…
2008
Abstract We studied the effect of leukotriene D(4) (LTD(4)) on a human bronchial epithelial cell line (16HBE) overexpressing the cysteinyl leukotriene (CysLT) (1) receptor (HBECysLT(1)R), looking at the associated signal transduction mechanisms as well as at effects on inflammatory cell adhesion. The results obtained showed that LTD(4) increases the phosphorylation of extracellular signal-regulated protein kinase (ERK) 1/2 and of the signal transducer and activator of transcription 1 (STAT-1) in serine 727 (STAT-1Ser727), resulting in increased eosinophil adhesion to HBECysLT(1)R, associated with enhanced surface expression of intercellular adhesion molecule (ICAM) 1. Pretreatment with a Cy…
Activation and translocation of p38 mitogen-activated protein kinase after stimulation of monocytes with contact sensitizers.
2002
Recently we described the induction of tyrosine phosphorylation by contact sensitizers as an early molecular event during the activation of antigen- presenting cells. In this study, the role of the p38 mitogen-activated protein kinase for the activation of human monocytes after exposure to four structurally unrelated contact sensitizers was analyzed in comparison with the irritant benzalkonium chloride and an inductor of oxidative stress (H 2 O 2 ) using immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay techniques. Bio chemical analysis revealed a translocation of p38 from the cytoplasm to the detergent-resistant cell fraction only upon stimulation with contact sen…