기초 : 톡소포자충 감염 신경교종세포의 Mitogen-Activated Protein Kinase Pathway 활성화

박병현 ( Byung Hyun Park ),이현성 ( Hyun Sung Lee ),이종수 ( Jong Soo Lee ),양승환 ( Seung Hwan Yang ),신대환 ( Dae Whan Shin ),이영하 ( Young Ha Lee ) 대한뇌종양학회 2006 대한뇌종양학회지 Vol.5 No.2

Objective:Gliomas are the most common primary brain tumors in adults. Toxoplasma gondii is an obligate intracellular parasite with a high affinity for brain cells. Mitogen-activated protein kinases(MAPKs) are known to regulate the host cell invasion, although little is known regarding MAPK signaling in Toxoplasma-infected glioma cells. Methods:U87MG and U373MG cells were infected with tachyzoites of the RH strain of T. gondii, and the kinetics of MAPK activation were determined by immunoblotting. We also determined the effects of MAPK inhibitors on glioma cell growth and T. gondii replication using the 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetraterazolium bromide(MTT; Sigma) method and [3H]-uracil incorporation assays. Results:There were no significant differences in the levels of unphosphorylated MAPK at different incubation times in the Toxoplasma-infected U373MG cells. T. gondii induced the activation of extracellular signal-regulated kinase(ERK) 1/2, p30MAPK, and c-Jun N-terminal kinase(JNK)1/2 within 30 minutes of infection, and showed differential kinetics of activation for each MAPK. The activation of ERK1/2, p38MAPK, and JNK1/2 in Toxoplasma-infected glioma cells was blocked by PD98059, SB202190, and SB203580, respectively. T. gondii replication was inhibited in a dose-dependent manner by the addition of MAPK inhibitors to Toxoplasma-infected glioma cells. Conclusion:Infection with T. gondii induces the activation of MAPKs in glioma cells, and this activation can be blocked by the addition of kinase-specific inhibitors. These results suggest that the MAPK pathway plays a role in the invasion of glioma cells with T. gondii.

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 Korean Society of Plant Pathology 2012 Plant Pathology Journal Vol.28 No.3

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.

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

Houjuan Xu,Xiaoxue Xu,Yujun Wang,비벡바지파이,Lisha Huang,Yongfang Chen,백광현 한국식물병리학회 2012 Plant Pathology Journal Vol.28 No.3

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.

Gene structure, molecular characterization and transcriptional expression of two p38 isoforms (MAPK11 and MAPK14) from rock bream (Oplegnathus fasciatus)

Umasuthan, N.,Bathige, S.D.N.K.,Noh, J.K.,Lee, J. Academic Press 2015 FISH AND SHELLFISH IMMUNOLOGY Vol.47 No.1

The p38 kinases are one of the four subgroups of mitogen-activated protein kinase (MAPK) superfamily which are involved in the innate immunity. The p38 subfamily that includes four members namely p38α (MAPK14), p38β (MAPK11), p38γ (MAPK12) and p38δ (MAPK13), regulates the activation of several transcription factors. In this study, a p38β (OfMAPK11) homolog and a p38α (OfMAPK14) homolog of Oplegnathus fasciatus were identified at genomic level. Results clearly showed that both MAPK11 and MAPK14 are well-conserved at both genomic structural- and amino acid (aa)-levels. Genomic sequences of OfMAPK11 (~15.6 kb) and OfMAPK14 (~13.4 kb) had 12 exons. A comparison of exon-intron structural arrangement of these genes from different vertebrate lineages indicated that all the exon lengths are highly conserved, except their terminal exons. Full-length cDNAs of OfMAPK11 (3957 bp) and OfMAPK14 (2504 bp) encoded corresponding proteins of 361 aa and 360 aa, respectively. Both OfMAPK proteins harbored a Ser/Thr protein kinases catalytic domain (S_TKc domain) which includes an activation loop with a dual phosphorylation site (TGY motif) and several specific-binding sites for ATP and substrates. Molecular modeling of the activation loop and substrate binding sites of rock bream MAPKs revealed the conservation of crucial residues and their orientation in 3D space. Transcripts of OfMAPKs were ubiquitously detected in eleven tissues examined, however at different levels. The modulation of OfMAPKs' transcription upon pathogen-associated molecular patterns (PAMPs: flagellin, lipopolysaccharide and poly I:C) and pathogens (Edwardsiella tarda, Streptococcus iniae and rock bream iridovirus) was investigated. Among the seven examined tissues, the flagellin-challenge upregulated the mRNA level of both OfMAPKs in the head kidney. Meanwhile, modulation of OfMAPK mRNA expression in the liver upon other immune-challenges varied in a time-dependent manner. Collectively, these results suggest that OfMAPKs are true members of p38 subfamily, which might be induced by different immune stimuli.

Rhythmic Expression of Mitogen Activated Protein Kinase Activity in Rice

Kudupudi Prabhakara Rao,Gubbala Vani,Kundan Kumar,Alok Krishna Sinha 한국분자세포생물학회 2009 Molecules and cells Vol.28 No.5

Mitogen activated protein kinase (MAPK) are known to get activated during various stress signals and transduce the message from the cell membrane to the nucleus for ap-propriate cellular reorganization. Though, a certain basal activity of MAPK is often observed in the control plants. Prolonged exposure of rice plants to lowered or elevated temperature exhibited a rhythm in the activation of MAPKs. We analyzed existence of a possible endogenous rhythm in the activity of MAPKs in rice plants. The plants growing at constant temperature entrained in 16/8 h day-night cycle showed diurnal rhythm in activity. When the activation of MAPK was tested under continuous conditions by shifting plants to continuous darkness for a period of 72 h, the periodic rhythm persisted and followed a circadian pattern. Analysis of the transcripts of group A, B and C members of MAPKs under above conditions by quantitative real time PCR revealed that the members of group C exhibit periodic rhythm. Our data indicates that the MAP kinase activity in rice follows rhythmic expression in a circadian manner.

Increased interaction between heat shock protein 27 and mitogen-activated protein kinase (p38 and extracellular signal-regulated kinase) in pre-eclamptic placentas

Shin, Jeong-Kyu,Jeong, Young-Taek,Jo, Hyun-Cheol,Kang, Min-Young,Chang, In-Suk,Baek, Jong-Chul,Park, Ji-Kwon,Lee, Soon-Ae,Lee, Jong-Hak,Choi, Wan-Sung,Paik, Won-Young Blackwell Publishing Asia 2009 JOURNAL OF OBSTETRICS AND GYNAECOLOGY RESEARCH -TO Vol.35 No.5

<P>Abstract</P><P>Aims: </P><P>Heat shock protein 27 (Hsp27) is a well-known stress response protein that is characterized by its phosphorylative capacity. Hsp27 becomes phosphorylated in response to various stimuli through interaction with several different kinases. The purpose of this study was to evaluate the interaction between Hsp27 and mitogen-activated protein kinase (MAPK) (p38, extracellular signal-regulated kinase [ERK], and c-Jun N-terminal kinase) in the human placenta derived from patients with pre-eclampsia.</P><P>Methods: </P><P>Western blot analysis was used to examine the levels of expression of Hsp27 and MAPK (p38, ERK, and c-Jun N-terminal kinase). Immunoprecipitation analysis was used to determine the interaction between Hsp27 and MAPK (p38 and ERK).</P><P>Results: </P><P>Western blotting analysis and immunohistochemistry showed that the expression of Hsp27 and p-Hsp27 in the placental tissues of the pre-eclampsia group were significantly higher than that in the normal pregnancy group. Immunoprecipitation analysis showed that the interaction between Hsp27 and MAPK (p38 and ERK) was significantly increased in the pre-eclamptic placenta tissues.</P><P>Conclusion: </P><P>The interaction between Hsp27 and MAPK was increased, suggesting that phosphorylation of Hsp27 might be induced by p38 and ERK in placentas from patients with pre-eclampsia.</P>

Bone Morphogenetic Protein 2-induced MAPKs Activation Is Independent of the Smad1/5 Activation

Jun, Ji Hae,Ryoo, Hyun-Mo,Woo, Kyung Mi,Kim, Gwan-Shik,Baek, Jeong-Hwa KOREAN ACADAMY OF ORAL BIOLOGY 2009 International Journal of Oral Biology Vol.34 No.2

Bone morphogenetic protein (BMP) 2 is a potent osteogenic factor. Although both Smad1/5 and mitogen-activated protein kinases (MAPKs) are activated by BMP2, the hierarchical relationship between them is unclear. In this study, we examined if BMP2-stimu1ated MAPK activation is regulated by Smad1/5 or vice versa. When C2C12 cells were treated with BMP2, the activation of extracellular signal-regulated kinasu (ERK), p38 MAPK and c-Jun-N-terminal kinase was evident within 5 min. The knockdown of both Smad1 and Smad5 by small interfering RNA did not affect the activation of these MAPKs. In addition, neither the overexpression of Smad1 nor Smad5 induced ERK activation. When ERK activation was induced by constitutively active MEK1 expression, the protein level and activation of Smad1 increased. Furthermore, the inhibition of constitutively active BMP receptor type IB-induced ERK activation significantly suppressed Smad1 activation. These results indicate that Smad1/5 activation is not necessary for BMP2-induced MAPK activation and also that ERK positively regulates Smad1 activation.

Inhibition of ERK and Activation of p38 are Involved in Diallyl Disulfide Induced Apoptosis of Leukemia HL-60 Cells

Hui Tan,Hui Ling,Jie He,Lan Yi,Jianguo Zhou,Min Lin,Qi Su 대한약학회 2008 Archives of Pharmacal Research Vol.31 No.6

We investigated the effects of diallyl disulfide (DADS) on the induction of apoptosis in human Leukemia cell line HL-60 and explored the roles of mitogen-activated protein kinase (ERK and p38 MAPK) pathways in the growth inhibition and apoptosis induced by DADS. MTT assay was used to determine the DADS induced cell growth inhibition in HL-60 cells. Flow cytometry and DNA fragmentation were used to examine the roles of apoptosis in DADS-mediated cell death. Western blot analysis of the expression of phospho-MAPKs (ERK and p38) was employed to elucidate the possible mechanisms of DADS induced apoptosis. We found that growth inhibition of HL-60 cells treated with DADS exhibited a dose-dependent response (P<0.05) and DADS induced significant apoptosis. DADS at the concentration of 10 mg/L persistently activated p38 and simultaneously reduced ERK activity. PD98059, an inhibitor of ERK upstream activators MAPK kinase MKK1 and MKK2, promoted cytotoxicity and apoptosis in HL-60 cells treated with DADS. In contrast, SB203580, an inhibitor of p38, decreased cytotoxicity and apoptosis induced by DADS. Therefore, DADS can effectively inhibit the proliferation and induce apoptosis of human leukemia cell line HL-60. Inhibition of ERK signaling pathways and activation of p38 signaling pathways are likely involved in DADS induced apoptosis in HL- 60 cells.

The highly pathogenic H5N1 avian influenza virus induces the mitogen-activated protein kinase signaling pathway in the trachea of two Ri chicken lines

부 티 하오,Hong Yeojin,Truong Anh Duc,Lee Sooyeon,Heo Jubi,Lillehoj,Hyun S.,홍영호 아세아·태평양축산학회 2022 Animal Bioscience Vol.35 No.7

Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry and economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for studies on HPAIV resistance. Therefore, in this study, we investigated gene expression related to the mitogen-activated protein kinase (MAPK) signaling pathway by comparing non-infected, HPAI-infected resistant, and susceptible Ri chicken lines. Methods: Resistant (Mx/A; BF2/B21) and susceptible Ri chickens (Mx/G; BF2/B13) were selected by genotyping the Mx and BF2 genes. Then, the tracheal tissues of non-infected and HPAIV H5N1 infected chickens were collected for RNA sequencing. Results: A gene set overlapping test between the analyzed differentially expressed genes (DEGs) and functionally categorized genes was performed, including biological processes of the gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. A total of 1,794 DEGs were observed between control and H5N1-infected resistant Ri chickens, 432 DEGs between control and infected susceptible Ri chickens, and 1,202 DEGs between infected susceptible and infected resistant Ri chickens. The expression levels of MAPK signaling pathway-related genes (including MyD88, NF-κB, AP-1, c-fos, Jun, JunD, MAX, c-Myc), cytokines (IL-1β, IL-6, IL-8), type I interferons (IFN-α, IFN-β), and IFNstimulated genes (Mx1, CCL19, OASL, and PRK) were higher in H5N1-infected than in non-infected resistant Ri chickens. MyD88, Jun, JunD, MAX, cytokines, chemokines, IFNs, and IFN-stimulated expressed genes were higher in resistant-infected than in susceptibleinfected Ri chickens. Conclusion: Resistant Ri chickens showed higher antiviral activity compared to susceptible Ri chickens, and H5N1-infected resistant Ri chickens had immune responses and antiviral activity (cytokines, chemokines, interferons, and IFN-stimulated genes), which may have been induced through the MAPK signaling pathway in response to H5N1 infection. Objective: The highly pathogenic avian influenza virus (HPAIV) is a threat to the poultry industry and economy and remains a potential source of pandemic infection in humans. Antiviral genes are considered a potential factor for studies on HPAIV resistance. Therefore, in this study, we investigated gene expression related to the mitogen-activated protein kinase (MAPK) signaling pathway by comparing non-infected, HPAI-infected resistant, and susceptible Ri chicken lines.Methods: Resistant (<i>Mx</i>/A; <i>BF2</i>/B21) and susceptible Ri chickens (<i>Mx</i>/G; <i>BF2</i>/B13) were selected by genotyping the <i>Mx</i> and <i>BF2</i> genes. Then, the tracheal tissues of non-infected and HPAIV H5N1 infected chickens were collected for RNA sequencing.Results: A gene set overlapping test between the analyzed differentially expressed genes (DEGs) and functionally categorized genes was performed, including biological processes of the gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. A total of 1,794 DEGs were observed between control and H5N1-infected resistant Ri chickens, 432 DEGs between control and infected susceptible Ri chickens, and 1,202 DEGs between infected susceptible and infected resistant Ri chickens. The expression levels of MAPK signaling pathway-related genes (including <i>MyD88</i>, <i>NF-κB</i>, <i>AP-1</i>, <i>c-fos</i>, <i>Jun</i>, <i>JunD</i>, <i>MAX</i>, <i>c-Myc</i>), cytokines (IL-1β, IL-6, IL-8), type I interferons (IFN-α, IFN-β), and IFN-stimulated genes (<i>Mx1</i>, <i>CCL19</i>, <i>OASL</i>, and <i>PRK</i>) were higher in H5N1-infected than in non-infected resistant Ri chickens. MyD88, Jun, JunD, MAX, cytokines, chemokines, IFNs, and IFN-stimulated expressed genes were higher in resistant-infected than in susceptible-infected Ri chickens.Conclusion: Resistant Ri chickens showed higher antiviral activity compared to susceptible Ri chickens, and H5N1-infected resistant Ri chickens had immune responses and antiviral activity (cytokines, chemokines, interferons, and IFN-stimulated genes), which may have been induced through the MAPK signaling pathway in response to H5N1 infection.

DJ-1 modulates the p38 mitogen-activated protein kinase pathway through physical interaction with apoptosis signal-regulating kinase 1

Mo, Jung-Soon,Jung, Jane,Yoon, Ji-Hye,Hong, Ji-Ae,Kim, Mi-Yeon,Ann, Eun-Jung,Seo, Mi-Sun,Choi, Yun-Hee,Park, Hee-Sae Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of cellular biochemistry Vol.110 No.1

<P>DJ-1 has been reported as a gene linked to early onset familial Parkinson's disease, and is functionally involved in transcriptional regulation and oxidative stress-induced cell death. To understand the role of DJ-1 in cellular stress, this study investigated DJ-1's effect on stress-activated protein kinase signaling and H<SUB>2</SUB>O<SUB>2</SUB>-induced activation of apoptosis signal-regulating kinase 1 (ASK1). According to the results, the overexpression of DJ-1 inhibited H<SUB>2</SUB>O<SUB>2</SUB>-induced activation of ASK1 as well as the activation of downstream kinases in the p38 mitogen-activated protein kinase (MAPK) signaling cascade. The results of both in vivo binding and kinase studies have revealed that ASK1 is the direct target of DJ-1, whereas it has shown no effect on either MKK3 or p38. DJ-1 blocked both the homo-oligomerization of ASK1 and inhibited ASK1 activity. Taken together, our data strongly suggest that DJ-1, by directly inhibiting ASK1, may act as a negative regulator in ASK1 signaling cascades. J. Cell. Biochem. 110: 229–237, 2010. © 2010 Wiley-Liss, Inc.</P>