• Title, Summary, Keyword: MAPK

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Specific Binding and Catalytic Activation of the MAPK-MKP Complex

  • Kim, Myeongbin;Ryu, Seong Eon
    • Biodesign
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    • v.6 no.4
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    • pp.79-83
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    • 2018
  • Mitogen-activated protein kinases (MAPKs) are one of the most important enzymes in various cellular activities, and the MAPK signaling pathway is implicated in many disorders. MAPK phosphatases (MKPs) are regulators that contain a MAPK-binding domain (MBD) for MAPK recognition, and a catalytic domain (CD), for dephosphorylation and inactivation of MAPKs. Due to their crucial role in regulating the MAPK pathway, MKPs are regarded as a potential drug target in various diseases. Attempts have also been made to regulate the MAPK pathway by reducing the MKP activity. For drug development, it is important to understand the key features of MAPK-MKP complex formation. This review summarizes the studies on MAPK-MKP complexes, mainly focusing on their selective recognition and catalytic activation.

Regulation of Mitogen Activated Protein Kinase Activity by Solubilized Matrigel in the Preimplantation Mouse Embryos (생쥐 착상 전 배아에서 용해된 Matrigel에 의한 Mitogen Activated Protein Kinase 활성의 조절)

  • 강병문;정병목;계명찬
    • Development and Reproduction
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    • v.6 no.1
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    • pp.1-6
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    • 2002
  • To elucidate the mechanism underlying the embryotropic effect of extracellular matrix(ECM) on the preimplantation development of mammalian embryos, the involvement of mitogen-activated protein kinase(MAPK) downstream the integrin signaling was examined in mouse blastocysts. Blastocysts were cultured in the presence of growth factor-reduced(GFR) Matrigel(0.5%, v/v). MAPK activity was measured by in vitro phosphorylation of myelin basic protein by the Erk1/2 antibody immunoprecipitates of embryonic extract following the Matrigei treatment. MAPK activity of the early blastocysts rapidly increased within 10 min fo1lowing the Matrigel treatment. When the embryos were cultured for 12 h in the presence of Matrigel, the MAPK activity was significantly higher than that ot the control embryos. PD098059, a MAPK kinase(MEK) inhibitor, attenuated the effect of Matrigel on the change in MAPK activity. Taken together, it suggested that the embryotropic effect of ECM proteins might be mediated by the activation of MAPK cascade.

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Regulation of Preimplantation Development of Mouse Embryos by Insulin and Tumor Necrosis Factor alpha (생쥐 초기배아에서 Insulin과 Tumor Necrosis Factor $\alpha$에 의한 발생의 조절)

  • 계명찬;한현주;최진국
    • Development and Reproduction
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    • v.5 no.2
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    • pp.101-106
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    • 2001
  • Present study was aimed to verify the role of insulin and TNF-$\alpha$ in development of preimplantation embryos. Mouse morula were cultured for 40 hr in the presence or absence of insulin(400 ng/ml) and TNF-$\alpha$ (50 ng/ml). The morphological development, cell number of blastomeres per blastocyst, and mitogen activated protein kinase(MAPK) activity were examined. The developmental rate and cell number per embryo were the highest in insulin treatment group and the lowest in TNF-$\alpha$ treatment group. There was no significant difference in developmental rate between control and insulin plus TNF-$\alpha$ group. Taken together, it suggested that TNF-$\alpha$ impaired embryonic development and that insulin rescued developmental impairment imposed by TNF-$\alpha$. In blastocysts, insulin treatment significantly increased MAPK activity. TNF-$\alpha$ decreased the MAPK activity in a concentration-dependent manner. In the TNF-$\alpha$(50 ng/ml) -primed embryos, activation of MAPK by insulin was attenuated. In conclusion, these results suggest that there was a cross talk between insulin and TNF-$\alpha$ by means of activation of MAPK in preimplantation embryos and that insulin might rescue damage of embryos exposed to TNF-$\alpha$.

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MAPK Activity in Porcine Oocytes Maturing InVitro (유사분열 활성화 단백질 효소가 돼지난자의 체외성숙에 미치는 영향)

  • Lee, Jae-Dal
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.11 no.6
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    • pp.2124-2128
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    • 2010
  • In this study, we determined effects of the mitogen-activated protein kinase (MAPK) inhibitor, U0126 on meiotic maturation, microtubule organization and actin filament assembly in the porcine oocyte. The phosphorylated MAPK was first detected at 12 h after the initiation of maturation cultures, fully activated at 24h, and remained until metaphase II. Treatment of germinal vesicle (GV) stage oocytes with $20{\mu}M$ U0126 completely blocked MAPK phosphorylation, but germinal vesicle breakdown (GVBD) was normally proceeded. However, the oocytes didn‘t progress to the metaphase I. The inhibition of MAPK resulted in abnormal spindles. In oocytes treated with U0126 after GVBD, polar body extrusion was normal, but the organization of the metaphase plate and chromosome segregation were abnormal. In conclusion, MAPK activity plays an important regulatory role in GV chromatin configuration and meiotic progress in porcine oocyte maturation.

A Novel MAP Kinase Gene in Cotton (Gossypium hirsutum L.), GhMAPK, is Involved in Response to Diverse Environmental Stresses

  • Wang, Meimei;Zhang, Ying;Wang, Jian;Wu, Xiaoliang;Guo, Xingqi
    • BMB Reports
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    • v.40 no.3
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    • pp.325-332
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    • 2007
  • The mitogen-activated protein kinase (MAPK) cascade is one of the major and evolutionally conserved signaling pathways and plays pivotal role in the regulation of stress and developmental signals in plants. Here, a novel gene, termed Gossypium hirsutum MAPK (GhMAPK), was isolated from cotton. The full-length cDNA of GhMAPK encodes for a 372 amino acid protein that contains all 11 of the MAPK conserved subdomains and the phosphorylationactivation motif, TEY. Amino acid sequence alignment revealed that GhMAPK shared high identity with group-C MAPK in plants and showed 83~89% similarities with MAPKs from Arabidopsis, apricot, pea, petunia, and tobacco. Southern blot analysis indicated that the GhMAPK belonged to a multygene family in cotton. Two introns were found within the region of genomic sequence. Northern blot analysis revealed that the transcripts of GhMAPK accumulated markedly when the cotton seedlings were subjected to various abiotic stimuli such as wounding, cold (4$^{\circ}C$), or salinity stress; Furthermore, GhMAPK was upregulated by the exogenous signaling molecules, such as salicylic acid (SA) and hydrogen peroxide ($H_2O_2C$), as well as pathogen attacks. These results indicate that the GhMAPK, which has a high degree of identity with group-C plant MAPKs, may also play an important role in response to environmental stresses.

Cross-talk between STAT6 and Ras/MAPK Pathway for the IL-4-mediated T Cell Survival

  • So, Eui-Young;Jang, Ji-Young;Lee, Choong-Eun
    • BMB Reports
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    • v.34 no.6
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    • pp.578-583
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    • 2001
  • As a prototypic Thl vs Th2 cytokine, IFN-$\gamma$ and IL-4 activate distinct STAT proteins, STAT1 and STATE, respectively. In cytokine-producing Jurkat T cells, IL-4 is effectively rescued from cell death that is induced by dexamethasone, but IFN-$\gamma$ failed to do so. Since the Ras/MAPK pathway is known to play an important role in cytokine-induced cell survival, we investigated the mechanism of T cell survival through the analysis of functional cross-talk between Ras/MAPK and distinct STAT proteins that are activated by IL-4 and IFN-$\gamma$. Although IL-4 and IFN-$\gamma$ each induced the activation of STATE and STATI. in Jurkat T cells, respectively, only IL-4 was capable of inducing MAPK. Along with tyrosine kinase inhibitors, MEK/MAPK inhibitors also caused a significant suppression of the IL-4-induced STATE activity. This suggests a positive regulation of STATE by MAPK during IL-4 signal transduction. Furthermore, transfection studies with dominant active (da) vs dominant negative (dn) Ras revealed that daRas, but not dnRas, selectively up-regulated the expression and activity of STATE with a concomitant increase in MAPK activity. These results, therefore, suggest that there is a functional cross-talk between the Ras/MAPK and Jak/STAT6 pathways, which may have a role in the IL-4-induced T cell survival.

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The Mitogen-Activated Protein Kinase Signal Transduction Pathways in Alternaria Species

  • Xu, Houjuan;Xu, Xiaoxue;Wang, Yu-Jun;Bajpai, Vivek K.;Huang, Lisha;Chen, Yongfang;Baek, Kwang-Hyun
    • 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.

c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) are involved in Mycobacterium tuberculosis-induced expression of Leukotactin-1

  • Cho, Jang-Eun;Park, Sang-Jung;Cho, Sang-Nae;Lee, Hye-Young;Kim, Yoon-Suk
    • BMB Reports
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    • v.45 no.10
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    • pp.583-588
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    • 2012
  • Leukotactin(Lkn)-1 is a CC chemokine and is upregulated in macrophages in response to Mycobacterium tuberculosis (MTB) infection. We investigated whether mitogen-activated protein kinases (MAPKs) are involved in MTB-induced expression of Lkn-1. The up-regulation of Lkn-1 by infection with MTB was inhibited in cells treated with inhibitors specific for JNK (SP600125) or p38 MAPK (SB202190). Since the up-regulation of Lkn-1 by MTB has been reported to be mediated by the PI3-K/PDK1/Akt signaling, we examined whether JNK and/or p38 MAPK are also involved in this signal pathway. MTB-induced Akt phosphorylation was blocked by treatment with JNK- or p38 MAPK-specific inhibitors implying that p38 and JNK are upstream of Akt. In addition, treatment with the PI3-K-specific inhibitor inhibited MTB-stimulated activation of JNK or p38 MAPK implying that PI3-K is upstream of JNK and p38 MAPK. These results collectively suggest that JNK and p38 MAPK are involved in the signal pathway responsible for MTB-induced up-regulation of Lkn-1.

Analysis of MAPK Signaling Pathway Genes in the Intestinal Mucosal Layer of Necrotic Eenteritis-Afflicted Two Inbred Chicken Lines

  • Truong, Anh Duc;Hong, Yeojin;Lee, Janggeun;Lee, Kyungbaek;Lillehoj, Hyun S.;Hong, Yeong Ho
    • Korean Journal of Poultry Science
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    • v.44 no.3
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    • pp.199-209
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    • 2017
  • Mitogen-activated protein kinase (MAPK) signaling pathways play a key role in innate immunity, inflammation, cell proliferation, cell differentiation, and cell death. The main objective of this study was to investigate the expression level of candidate MAPK pathway genes in the intestinal mucosal layer of two genetically disparate chicken lines (Marek's disease-resistant line 6.3 and Marek's disease-susceptible line 7.2) induced with necrotic enteritis (NE). Using high-throughput RNA sequencing, we investigated 178 MAPK signaling pathway related genes that were significantly and differentially expressed between the intestinal mucosal layers of the NE-afflicted and control chickens. In total, 15 MAPK pathway genes were further measured by quantitative real-time PCR(qRT-PCR) and the results were consistent with the RNA-sequencing data. All 178 identified genes were annotated through Gene Ontology and mapped onto the KEGG chicken MAPK signaling pathway. Several key genes of the MAPK pathway, ERK1/2, JNK1-3, p38 MAPK, MAP2K1-4, $NF-{\kappa}B1/2$, c-Fos, AP-1, Jun-D, and Jun, were differentially expressed in the two chicken lines. Therefore, we believe that RNA sequencing and qRT-PCR analysis provide resourceful information for future studies on MAPK signaling of genetically disparate chicken lines in response to pathogens.

THE EFFECT OF PKC PATHWAY & MAPK PATHWAY ON RUNX2 TRANSCRIPTIONAL ACTIVITY (Protein kinase C 및 MAPK pathway가 Runx2의 전사 활성에 미치는 영향)

  • Kim, Eun-Jung;Kim, Hyun-Jung;Ryoo, Hyun-Mo;Kim, Hyun-Jung;Kim, Young-Jin;Nam, Soon-Hyeun
    • THE JOURNAL OF THE KOREAN ACADEMY OF PEDTATRIC DENTISTRY
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    • v.29 no.3
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    • pp.337-344
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    • 2002
  • Runx2, a Runt-related osteoblast-specific transcription factor, is essential for osteoblast differentiation and function. Runx2 was identified as a key regulator of osteoblast-specific gene expression through its binding to the OSE2 element present in these genes. However, little is known about the signaling mechanism regulating Runx2 activity. This study examines the role of protein kinase C (PKC) pathway and mitogen-activated protein kinase (MAPK) pathway in regulating Runx2 and bone marker genes (osteopontin; OP, osteocalcin; OC). Luciferase assay and Northern blot analysis suggested that the stimulation of PKC by PMA increased transcription activity of Runx2 and bone marker genes (OP and OC) and also increased expression of Runx2. The stimulation of MAPK by okadaic acid increased transcription activity of Runx2 and bone marker genes (OP and OC). Pretreatment with PD98059 (Erk pathway inhibitor) and SB203580 (P38 pathway inhibitor) prior to PMA treatment decreased PMA stimulated Runx2 activity. Together these results indicate that both PKC and MAPKs are involved in the regulation of Runx2 activity and also the stimulation of Runx2 transcriptional activity by the PKC pathway is through activation of MAPK pathway.

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