• The Plant Pathology Journal
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• v.26 no.2
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• pp.101-109
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• 2010

Protein phosphorylation is one of the major mechanisms for controlling many cellular processes in all living organisms. Mitogen-activated protein kinase (MAPK) cascades are known to transducer extracellular stimuli to several cellular processes, including cell division, differentiation as well as responses to various stresses. In plants, several studies have revealed that MAPK cascade pathways play an important role in responses against biotic and abiotic stresses, including wounding, pathogen infection, temperature, drought, salinity and plant hormones. It is also known that MAPK cascades-mediated signaling is an essential process in the resistance step to pathogens by regulating the activity of transcription factors. Here, the insights into the functions of MAPK cascade pathways in plant defense response signaling from Arabidopsis, tobacco and rice are described.

• The Plant Pathology Journal
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• v.28 no.3
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• pp.227-238
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• 2012

Mitogen-activated protein kinase (MAPK) cascades are conserved signaling modules in the eukaryotic cells. They are involved in many major cell processes in fungi such as stress responses, vegetative growth, pathogenicity, secondary metabolism and cell wall integrity. In this review, we summarized the advances of research on the MAPK signaling pathways in Alternaria species. As major phytopathogenic fungi, Alternaria species reduce crop production. In contrast to the five MAPK pathways known in yeast, only three MAPK pathways as Fus3/Kss1-type, Hog1-type, and Slt2-type have been characterized in Alternaria. The Fus3/Kss1-type MAPK pathway participates in regulation of vegetative growth, conidiation, production of some cell-wall-degrading enzymes and pathogenicity. The Hog1-type pathway is involved in osmotic and oxidative stress, fungicides susceptibility and pathogenicity. The Slt2-type MAP kinases play an important role on maintaining cell wall integrity, pathogenicity and conidiation. Although recent advances on the MAPK pathways in Alternaria spp. reveal many important features on the pathogenicity, there are many unsolved problems regarding to the unknown MAP kinase cascade components and network among other major signal transduction. Considering the economic loss induced by Alternaria spp., more researches on the MAPK pathways will need to control the Alternaria diseases.

• Parasites, Hosts and Diseases
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• v.53 no.4
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• pp.371-377
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• 2015

Trichomonas vaginalis induces proinflammation in cervicovaginal mucosal epithelium. To investigate the signaling pathways in $TNF-{\alpha}$ production in cervical mucosal epithelium after T. vaginalis infection, the phosphorylation of PI3K/AKT and MAPK pathways were evaluated in T. vaginalis-infected SiHa cells in the presence and absence of specific inhibitors. T. vaginalis increased $TNF-{\alpha}$ production in SiHa cells, in a parasite burden-dependent and incubation time-dependent manner. In T. vaginalis-infected SiHa cells, AKT, ERK1/2, p38 MAPK, and JNK were phosphorylated from 1 hr after infection; however, the phosphorylation patterns were different from each other. After pretreatment with inhibitors of the PI3K/AKT and MAPK pathways, $TNF-{\alpha}$ production was significantly decreased compared to the control; however, $TNF-{\alpha}$ reduction patterns were different depending on the type of PI3K/MAPK inhibitors. $TNF-{\alpha}$ production was reduced in a dose-dependent manner by treatment with wortmannin and PD98059, whereas it was increased by SP600125. These data suggested that PI3K/AKT and MAPK signaling pathways are important in regulation of $TNF-{\alpha}$ production in cervical mucosal epithelial SiHa cells. However, activation patterns of each pathway were different from the types of PI3K/MAPK pathways.

• Toxicological Research
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• v.35 no.1
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• pp.93-101
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• 2019

Tetrabromobisphenol A (TBBPA), the most common industrial brominated flame retardant, acts as a cytotoxic, neurotoxic, and immunotoxicant, causing inflammation and tumors. However, the mechanism of TBBPA-induced matrix metalloproteinase-9 (MMP-9) expression in human breast cancer cells is not clear. In human breast cancer MCF-7 cells, treatment with TBBPA significantly induced the expression and promoter activity of MMP-9. Transient transfection with MMP-9 mutation promoter constructs verified that $NF-{\kappa}B$ and AP-1 response elements are responsible for the effects of TBBPA. Furthermore, TBBPA-induced MMP-9 expression was mediated by $NF-{\kappa}B$ and AP-1 transcription activation as a result of the phosphorylation of the Akt and MAPK signaling pathways. Moreover, TBBPA-induced activation of Akt/MAPK pathways and MMP-9 expression were attenuated by a specific NADPH oxidase inhibitor, and the ROS scavenger. These results suggest that TBBPA can induce cancer cell metastasis by releasing MMP-9 via ROS-dependent MAPK, and Akt pathways in MCF-7 cells.

• Plant Biotechnology Reports
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• v.5 no.1
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• pp.19-25
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• 2011

Tocopherols belong to the plant-derived poly phenolic compounds known for antioxidant functions in plants and animals. Activation of mitogen-activated protein kinases (MAPK) is a common reaction of plant cells in defense-related signal transduction pathways. We report a novel non-antioxidant function of ${\alpha}$-tocopherol in higher plants linking the physiological role of tocopherol with stress signalling pathways. Pre-incubation of a low concentration of $50{\mu}M$ ${\alpha}$-tocopherol negatively interferes with MAPK activation in elicitor-treated tobacco BY2 suspension culture cells and wounded tobacco leaves, whereas pre-incubated BY2 cells with ${\alpha}$-tocopherol phosphate did not show the inhibitory effect on stimuli-induced MAPK activation. The decreased MAPK activity was neither due to a direct inhibitory effect of ${\alpha}$-tocopherol nor due to the induction of an inhibitory or inactivating activity directly affecting MAPK activity. The data support that the target of ${\alpha}$-tocopherol negatively regulates an upstream component of the signaling pathways that leads to stress dependent MAPK activation.

• Mycobiology
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• v.45 no.4
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• pp.362-369
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• 2017

We assessed the regulation of cryparin, a class II hydrophobin, using three representative mitogen-activated protein kinase (MAPK) pathways in Cryphonectria parasitica. Mutation of the CpSlt2 gene, an ortholog of yeast SLT2 in the cell wall integrity (CWI) pathway, resulted in a dramatic decrease in cryparin production. Similarly, a mutant of the CpBck1 gene, a MAP kinase kinase kinase gene in the CWI pathway, showed decreased cryparin production. Additionally, mutation of the cpmk1 gene, an ortholog of yeast HOG1, showed decreased cryparin production. However, mutation of the cpmk2 gene, an ortholog of yeast Kss1/Fus3, showed increased cryparin production. The easy-wet phenotype and accumulation of the cryparin transcript in corresponding mutants were consistent with the cryparin production results. In silico analysis of the promoter region of the cryparin gene revealed the presence of binding motifs related to downstream transcription factors of CWI, HOG1, and pheromone responsive pathways including MADS-box- and Ste12-binding domains. Real-time reverse transcriptase PCR analyses indicated that both CpRlm1, an ortholog of yeast RLM1 in the CWI pathway, and cpst12, an ortholog of yeast STE12 in the mating pathway, showed significantly reduced transcription levels in the mutant strains showing lower cryparin production in C. prasitica. However, the transcription of CpMcm1, an ortholog of yeast MCM1, did not correlate with that of the mutant strains showing downregulation of cryparin. These results indicate that three representative MAPK pathways played a role in regulating cryparin production. However, regulation varied depending on the MAPK pathways: the CWI and HOG1 pathways were stimulatory, whereas the pheromone-responsive MAPK was repressive.

• Molecules and Cells
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• v.25 no.3
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• pp.397-406
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• 2008

Computational modeling of signal transduction is currently attracting much attention as it can promote the understanding of complex signal transduction mechanisms. Although several mathematical models have been used to examine signaling pathways, little attention has been given to crosstalk mechanisms. In this study, an attempt was made to develop a computational model for the pathways involving growth-factor-mediated mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3'-kinase/protein kinase B (PI3K/Akt). In addition, the dynamics of the protein activities were analyzed based on a set of kinetic data. The simulation approach integrates the information on several levels and predicts systems behavior. The in-silico analysis conducted revealed that the Raf and Akt pathways act independently.

• Molecules and Cells
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• v.39 no.1
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• pp.40-45
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• 2016

Peroxiredoxins are highly conserved and abundant peroxidases. Although the thioredoxin peroxidase activity of peroxiredoxin (Prx) is important to maintain low levels of endogenous hydrogen peroxide, Prx have also been shown to promote hydrogen peroxide-mediated signalling. Mitogen activated protein kinase (MAPK) signalling pathways mediate cellular responses to a variety of stimuli, including reactive oxygen species (ROS). Here we review the evidence that Prx can act as both sensors and barriers to the activation of MAPK and discuss the underlying mechanisms involved, focusing in particular on the relationship with thioredoxin.

• Journal of Plant Biotechnology
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• v.49 no.4
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• pp.300-306
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• 2022

The mitogen-activated protein kinase (MAPK) signaling cascade is essential for a wide range of cellular responses in plants, including defense responses, responses to abiotic stress, hormone signaling, and developmental processes. Recent investigations have shown that the stress, ethylene, and MAPK signaling pathways negatively affect the formation of nitrogen-fixing nodules by directly modulating the symbiotic signaling components. However, the molecular mechanisms underlying the defense responses mediated by MAPK signaling in the organogenesis of nitrogen-fixing nodules remain unclear. In the present study, I demonstrate that the Medicago truncatula mitogen-activated protein kinase kinase 5 (MtMKK5)-Medicago truncatula mitogen-activated protein kinase 3/6 (MtMPK3/6) signaling module, expressed specifically in the symbiotic nodules, promotes defense signaling, but not ethylene signaling pathways, thereby inhibiting nodule development in M. truncatula. U0126 treatment resulted in increased cell division in the nodule meristem zone due to the inhibition of MAPK signaling. The phosphorylated TEY motif in the activation domain of MtMPK3/6 was the target domain associated with specific interactions with MtMKK5. I have confirmed the physical interactions between M. truncatula nodule inception (MtNIN) and MtMPK3/6. In the presence of high expression levels of the defense-related genes FRK1 and WRKY29, MtMKK5a overexpression significantly enhanced the defense responses of Arabidopsis against Pseudomonas syringae pv. tomato DC3000 (Pst DC3000). Overall, my data show that the negative regulation of symbiotic nitrogen-fixing nodule organogenesis by defense signaling pathways is mediated by the MtMKK5-MtMPK3/6 module.

• IMMUNE NETWORK
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• v.11 no.2
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• pp.123-133
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• 2011

Background: Mycobacterium tuberculosis (Mtb) heparin binding hemagglutinin (HBHA) is an Ag known to evoke effective host immune responses during tuberculosis infection. However, the molecular basis of the host immune response to HBHA has not been fully characterized. In this study, we examined the molecular mechanisms by which HBHA can induce the expression of proinflammatory cytokines in macrophages. Methods: HBHA-induced mRNA and protein levels of proinflammatory cytokines were determined in bone marrow-derived macrophages (BMDMs) using RT-PCR and ELISA analysis. The roles of intracellular signaling pathways for NF-${\kappa}B$, PI3-K/Akt, and MAPKs were investigated in macrophage proinflammatory responses after stimulation with HBHA. Results: HBHA robustly activated the expression of mRNA and protein of both TNF-${\alpha}$ and IL-6, and induced phosphorylation of NF-${\kappa}B$, Akt, and MAPKs in BMDMs. Both TNF-${\alpha}$ and IL-6 production by HBHA was regulated by the NF-${\kappa}B$, PI3-K, and MAPK pathways. Furthermore, PI3-K activity was required for the HBHA-induced activation of ERK1/2 and p38 MAPK, but not JNK, pathways. Conclusion: These data suggest that mycobacterial HBHA significantly induces proinflammatory responses through crosstalk between the PI3-K and MAPK pathways in macrophages.