Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.24 (mitogen-activated protein kinase)
 95,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mitogen-activated protein kinases (MAPKs) are evolutionary conserved enzymes connecting cell-surface receptors to critical regulatory targets within cells. The three major MAPK cascades are known, the extracellular signal-regulated protein kinase (ERK) cascade, c-Jun amino-terminal protein kinase/stress-activated protein kinase (JNK/SAPK) cascade and p38-MAPK cascade. This paper is focused on characterization of these MAPK cascades in terms of their distribution and biological role in some pathological processes (apoptosis, hypertrophy) with a special orientation on the role of MAPKs in cardiovascular system during ischemia/reperfusion.
Gen Physiol Biophys 2002 Sep
PMID:Mitogen-activated protein kinases and their role in regulation of cellular processes. 1253 49

The temporal and spatial distribution of active c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) in the brain was investigated in an experimental virus-mouse system in which neurovirulent influenza A virus caused lethal acute encephalitis. Following stereotaxic microinjection into the olfactory bulb, virus-infected neurons appeared in several midbrain structures, including the ventral tegmental area, amygdala and the pyramidal layer of the hippocampus. Infected neurons exhibited apoptosis on day 5, as demonstrated by in situ detection of DNA fragmentation and active caspase-3. The stress-responsive JNK signal transduction pathway was activated in virus-infected neurons. Activation of p38 MAPK was widespread and occurred in astrocytes on day 7 after infection. Active p38 MAPK in astrocytes showed no association with apoptosis but appeared to be involved in regulation of TNF-alpha production. These results indicate that these two stress-activated protein kinases may play distinct roles during the course of lethal acute influenza virus encephalitis.
J Gen Virol 2003 Sep
PMID:Differential activation of the c-Jun N-terminal kinase/stress-activated protein kinase and p38 mitogen-activated protein kinase signal transduction pathways in the mouse brain upon infection with neurovirulent influenza A virus. 1291 61

Yaba-like disease virus (YLDV) genes 7L and 145R are located on opposite ends of the genome and are predicted to encode 7-transmembrane proteins (7-TM) that share 53 and 44 % amino acid identity, respectively, to human CC chemokine receptor 8 (hCCR8). In this report, we demonstrate that early after infection with YLDV, cells acquire the ability to bind human CCL1. By expression of genes 7L and 145R in vaccinia virus, we demonstrated that each protein is glycosylated and is exposed on the cell surface with the N terminus outside the cell. Protein 7L, but not 145R, is able to bind hCCL1 (K(d)=0.6+/-0.13 nM) and couple to heterotrimeric G-proteins and to activate the extracellular signal-regulated kinases (ERK1/2). 7L binds several chemokines including the viral chemokines vMIPI and vMIPII and hCCL7/MCP3. This binding seems species-specific as 7L does not bind the murine orthologues of CCL1 and CCL7 in the assays used. This represents the first example of a poxviral 7-TM chemokine receptor that has functional interactions with a human chemokine.
J Gen Virol 2003 Dec
PMID:Yaba-like disease virus protein 7L is a cell-surface receptor for chemokine CCL1. 1464 13

Estrogens affect the functioning of several non-reproductive tissues, the immune system in particular. In mammalian immunocytes, 17beta-estradiol (E2) has both dose- and cell-type specific effects and the responses to E2 seem to be mediated by rapid, non-genomic mechanisms; these may be initiated at either membrane or cytosolic locations, and can result in both direct local effects, such as modification of ion fluxes, and regulation of gene transcription secondary to activation of different kinase cascades, including mitogen activated protein kinases (MAPKs). In this work, the short-term effects of E(2) and the possible mechanisms of estrogen-mediated cell signaling were investigated in the hemocytes, the immune cells of the bivalve mollusc, the mussel Mytilus galloprovincialis Lam. The results show that E2 (25nM) caused a rapid and significant increase in hemocyte cytosolic [Ca2+]; lower concentrations (5 nM) showed a smaller, not significant effect. Both E2 concentrations affected the phosphorylation state of the components of tyrosine kinase-mediated signal transduction MAPK- and STAT- (signal transducers and activators of transcription) like proteins within 5-15 min from E2 addition. A greater effect and clearer time course were observed with 25 nM E2: in particular, E2 induced a transient increase in p-ERK2 MAPK and a persistent increase in p-p38 MAPK. Moreover, both STAT3 and STAT5 were tyrosine phosphorylated in response to E2. E2 (5 nM) induced both morphological (as evaluated by SEM) and functional changes (such as extracellular release of hydrolytic enzymes, lysosomal membrane destabilisation, and stimulation of the bactericidal activity) within 10-30 min from addition. Lysosomal membrane destabilisation induced by both E2 concentrations was abolished by hemocyte preincubation with the p38 MAPK inhibitor SB203580, and significantly reduced by PD98059 and Wortmannin (inhibitors of ERK MAPK and PI3-K, respectively), this suggesting that rapid activation of kinase cascades is involved in mediating the effects of E2 in mussel hemocytes. The antiestrogen Tamoxifen prevented or strongly reduced most, but not all, the effects of E2. Western blotting with heterologous anti-ERalpha-anti-ERbeta-antibodies revealed the presence of immunoreactive ERalpha- and ERbeta-like proteins in hemocyte protein extracts. Overall, our data support the hypothesis that the rapid effects and mechanisms of action of 17beta-estradiol are extremely conserved and that they may play a crucial role in endocrine-immune interactions in invertebrates.
Gen Comp Endocrinol 2004 Mar
PMID:Rapid effects of 17beta-estradiol on cell signaling and function of Mytilus hemocytes. 1498 Jul 97

Stimulation of the Jun NH(2)-terminal kinase/stress-activated protein kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase (p38/MAPK) is part of the stress-related signal transduction pathways conveying signals from the cell surface into the nucleus in order to initiate programmes of gene expression. Here, it was shown that infection by varicella-zoster virus (VZV) caused a 34-fold increase in activation of JNK/SAPK in the early phase of infection and a 2-fold increase in activation of p38/MAPK in the later phase. The phosphorylation of downstream targets c-Jun and ATF-2 was also increased; subsequent cascades to induce pro-inflammatory responses were significantly activated whereas cascades to activate apoptotic events were not. In the late phase of infection, both JNK/SAPK and p38/MAPK activities were reduced to basal levels. The use of specific inhibitors demonstrated that inhibition of JNK/SAPK resulted in a 2-fold increase in VZV replication whereas a strong decrease in virus replication was observed after inhibition of p38/MAPK. In contrast, constitutive activation of JNK/SAPK resulted in a decline in VZV replication. Blocking gene expression by treating cells with actinomycin D or cycloheximide prior to infection resulted in activation of neither JNK/SAPK nor p38/MAPK. It was assumed that the presence of tegument proteins was not sufficient to activate stress pathways, but that expression of viral genes was necessary. This suggests that activation of stress pathways by VZV infection represents a finely regulated system that activates cellular transcription factors for transregulation of VZV-encoded genes, but prevents activation of cellular defence mechanisms.
J Gen Virol 2004 Dec
PMID:Replication of varicella-zoster virus is influenced by the levels of JNK/SAPK and p38/MAPK activation. 1555 26

As the biochemical detection of bovine papillomavirus type 4 E5 is problematic, a fusion form of E5 and the green fluorescent protein (GFP-E5) was constructed and its characteristics were examined. GFP-E5 was detected in cells by autofluorescence and immunoblotting. Like wild-type (wt) E5, GFP-E5 localized in the endomembranes and permitted anchorage-independent (AI) growth. However, unlike wt E5, cells expressing GFP-E5 became quiescent in low serum and failed to sustain expression of cyclins D1 and to inactivate retinoblastoma protein (pRb). The normal anchorage requirement for cyclin D1 and cyclin A expression was abolished in cells expressing wt E5 or GFP-E5, residual extracellular signal-regulated kinase (ERK 1/2) activity was not required to sustain cyclin D1 and cyclin A expression in suspension and deregulation of cyclin A-cyclin-dependent kinase (CDK) activity was sufficient to account for AI growth of cells expressing E5. Constitutive upregulation of the CDK inhibitor p27(KIP1), characteristic of cells expressing wt E5, was not observed in those expressing GFP-E5; therefore, p27(KIP1) deregulation is not required for E5-mediated AI growth.
J Gen Virol 2004 Dec
PMID:Cyclin A expression and growth in suspension can be uncoupled from p27 deregulation and extracellular signal-regulated kinase activity in cells transformed by bovine papillomavirus type 4 E5. 1555 31

The phosphorylation status of the small hydrophobic (SH) protein of respiratory syncytial virus (RSV) was examined in virus-infected Vero cells. The SH protein was isolated from [35S]methionine- and [33P]orthophosphate-labelled RSV-infected cells and analysed by SDS-PAGE. In each case, a protein product of the expected size for the SH protein was observed. Phosphoamino acid analysis and reactivity with the phosphotyrosine specific antibody PY20 showed that the SH protein was modified by tyrosine phosphorylation. The role of tyrosine kinase activity in SH protein phosphorylation was confirmed by the use of genistein, a broad-spectrum tyrosine kinase inhibitor, to inhibit SH protein phosphorylation. Further analysis showed that the different glycosylated forms of the SH protein were phosphorylated, as was the oligomeric form of the protein. Phosphorylation of the SH protein was specifically inhibited by the mitogen-activated protein kinase (MAPK) p38 inhibitor SB203580, suggesting that SH protein phosphorylation occurs via a MAPK p38-dependent pathway. Analysis of virus-infected cells using fluorescence microscopy showed that, although the SH protein was distributed throughout the cytoplasm, it appeared to accumulate, at low levels, in the endoplasmic reticulum/Golgi complex, confirming recent observations. However, in the presence of SB203580, an increased accumulation of the SH protein in the Golgi complex was observed, although other virus structures, such as virus filaments and inclusion bodies, remained largely unaffected. These results showed that during RSV infection, the SH protein is modified by an MAPK p38-dependent tyrosine kinase activity and that this modification influences its cellular distribution.
J Gen Virol 2005 Feb
PMID:The respiratory syncytial virus small hydrophobic protein is phosphorylated via a mitogen-activated protein kinase p38-dependent tyrosine kinase activity during virus infection. 1565 57

Latent membrane protein 2A (LMP2A) of Epstein-Barr virus (EBV) shares protein motifs with the B-cell receptor that play a role in B-cell receptor signalling and has been shown to mimic an activated B-cell receptor by providing a survival signal for mature B cells in transgenic mice. Conversely, LMP2A has been reported not to support but to inhibit B-cell receptor signalling with respect to virus reactivation and to block lytic virus induction after anti-Ig treatment of EBV-infected B cells. To solve this apparent paradox, the role of LMP2A in lytic-cycle induction was re-examined in B cells conditionally immortalized by EBV. It was shown that, in the absence of other stimuli, LMP2A expression alone could lead to induction of the virus lytic cycle. Similarly to B-cell receptor stimulation by anti-Ig treatment, this LMP2A-mediated reactivation was dependent on the mitogen-activated protein kinase pathway and could be inhibited by the viral LMP1. Our data reinforce the notion that LMP2A is a functional homologue of the B-cell receptor, not only with respect to B-cell survival but also with respect to regulation of the lytic cycle.
J Gen Virol 2005 Mar
PMID:Epstein-Barr virus latent membrane protein 2A mimics B-cell receptor-dependent virus reactivation. 1572 14

Hepatitis C virus non-structural NS5A protein inhibits epidermal growth factor (EGF)-stimulated activation of the Ras-ERK mitogen-activated protein kinase pathway at a point upstream of Ras activation. To determine the mechanism of this inhibition, the events occurring between the EGF receptor and Ras in Huh-7 cells harbouring the HCV subgenomic replicon were investigated. It was shown that, following EGF stimulation, these cells exhibited decreased EGF receptor tyrosine phosphorylation, aberrant recruitment of the adaptor proteins ShcA and Grb2 to the EGF receptor, reduced phosphorylation of ShcA and reduced Ras activation in comparison with control cells. These data are consistent with effects of NS5A and/or other components of the replicon on multiple events occurring upstream of Ras.
J Gen Virol 2005 Apr
PMID:Perturbation of epidermal growth factor receptor complex formation and Ras signalling in cells harbouring the hepatitis C virus subgenomic replicon. 1578 96

Varicella-zoster virus (VZV) is ultimately dependent upon its host cell for replication. To ensure its reproduction, VZV reorganizes various cellular functions by taking advantage of pre-existing signalling pathways. Recently, it was demonstrated that the activation of stress-related mitogen-activated protein kinase pathways following infection led to increased phosphorylation of cellular transcription factors involved in VZV gene expression. Here, it was shown that members of the extracellular signal-regulated kinase (ERK) pathway are also influenced following VZV infection: c-Raf remained inactive in infected MeWo cells, whereas MEK1/2 and ERK1/2 were phosphorylated transiently, reaching their highest level of phosphorylation at between 10 and 12 h post-infection. Inhibition of this pathway resulted in a severe reduction in viral progeny and in an increased apoptotic response, indicating that the functionality of this cascade is essential for successful high-rate replication. In addition, the activities of Bad, a cytoplasmic target of ERK via ribosomal S6 kinase, and the nuclear-localized target c-Myc were analysed. Bad is a member of the Bcl-2 family and has a key function in regulating apoptosis. Pro-apoptotic functions of Bad are repressed by phosphorylation. A 10-fold increase in Bad phosphorylation at Ser-112 was detected following infection, which was suppressed after inhibition of ERK. The transcription factor c-Myc is involved in the regulation of cell growth and apoptosis. By performing immunoblots and quantitative RT-PCR, suppression of c-Myc expression was demonstrated at both the transcriptional and translational levels in VZV-infected cells. These results suggest that VZV optimizes the conditions for its replication in different ways: upregulation of proviral-acting systems and suppression of potentially antiviral-acting systems.
J Gen Virol 2006 Apr
PMID:Varicella-zoster virus influences the activities of components and targets of the ERK signalling pathway. 1652 22


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