Mycoparasitism is a key feature of Trichoderma (Hypocreales, Ascomycota) biocontrol agents. Recent studies of intracellular signal transduction pathways of the potent mycoparasite Trichoderma atroviride revealed the involvement of Tmk1, a mitogen-activated protein kinase (MAPK), in triggering the mycoparasitic response. We previously showed that mutants missing Tmk1 exhibit reduced mycoparasitic activity against several plant pathogenic fungi. In this study, we identified the most robustly regulated targets that were governed by Tmk1 during mycoparasitism using transcriptome and proteome profiling. Tmk1 mainly exerts a stimulating function for T. atroviride during its mycoparasitic interaction with the fungal plant pathogen Rhizoctonia solani, as reflected by 89% of strongly differently responding genes in the ∆tmk1 mutant compared to the wild type. Specifically, 54% of these genes showed strong downregulation in the response with a deletion of the tmk1 gene, whereas in the wild type the same genes were strongly upregulated during the interaction with the fungal host. These included the gene encoding the mycoparasitism-related proteinase Prb1; genes involved in signal transduction pathways such as a candidate coding for a conserved 14-3-3 protein, and a gene coding for Tmk2, the T. atroviride cell-wall integrity MAP kinase; genes encoding a specific siderophore synthetase, and multiple FAD-dependent oxidoreductases and aminotransferases. Due to the phosphorylating activity of Tmk1, different (phospho-)proteomics approaches were applied and identified proteins associated with cellular metabolism, energy production, protein synthesis and fate, and cell organization. Members of FAD- and NAD/NADP-binding-domain proteins, vesicular trafficking of molecules between cellular organelles, fungal translational, as well as protein folding apparatus were among others found to be phosphorylated by Tmk1 during mycoparasitism. Outstanding downregulation in the response of the ∆tmk1 mutant to the fungal host compared to the wild type at both the transcriptome and the proteome levels was observed for nitrilase, indicating that its defense and detoxification functions might be greatly dependent on Tmk1 during T. atroviride mycoparasitism. An intersection network analysis between the identified transcripts and proteins revealed a strong involvement of Tmk1 in molecular functions with GTPase and oxidoreductase activity. These data suggest that during T. atroviride mycoparasitism this MAPK mainly governs processes regulating cell responses to extracellular signals and those involved in reactive oxygen stress.

• MeSH
• Hypocreales * metabolismus   MeSH
• mitogenem aktivované proteinkinasy genetika   metabolismus   MeSH
• proteom metabolismus   MeSH
• regulace genové exprese u hub MeSH
• signální transdukce MeSH
• Trichoderma * metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mitogenem aktivované proteinkinasy MeSH
• proteom MeSH

Leguminous plants have established mutualistic endosymbiotic interactions with nitrogen-fixing rhizobia to secure nitrogen sources in root nodules. Before nodule formation, the development of early symbiotic structures is essential for rhizobia docking, internalization, targeted delivery, and intracellular accommodation. We recently reported that overexpression of stress-induced mitogen-activated protein kinase (SIMK) in alfalfa affects root hair, nodule, and shoot formation, raising the question of how SIMK modulates these processes. In particular, detailed subcellular spatial distribution, activation, and developmental relocation of SIMK during early stages of alfalfa nodulation remain unclear. Here, we characterized SIMK distribution in Ensifer meliloti-infected root hairs using live-cell imaging and immunolocalization, employing alfalfa stable transgenic lines with genetically manipulated SIMK abundance and kinase activity. In the SIMKK-RNAi line, showing down-regulation of SIMKK and SIMK, we found considerably decreased accumulation of phosphorylated SIMK around infection pockets and infection threads. However, this was strongly increased in the GFP-SIMK line, constitutively overexpressing green fluorescent protein (GFP)-tagged SIMK. Thus, genetically manipulated SIMK modulates root hair capacity to form infection pockets and infection threads. Advanced light-sheet fluorescence microscopy on intact plants allowed non-invasive imaging of spatiotemporal interactions between root hairs and symbiotic E. meliloti, while immunofluorescence detection confirmed that SIMK was activated in these locations. Our results shed new light on SIMK spatiotemporal participation in early interactions between alfalfa and E. meliloti, and its internalization into root hairs, showing that local accumulation of active SIMK modulates early nodulation in alfalfa.

• Klíčová slova
• Ensifer meliloti, Alfalfa, MAPKs, SIMK, immunolocalization, infection pocket, infection thread, light-sheet fluorescence microscopy, root hairs, subcellular localization,
• MeSH
• Medicago sativa genetika   metabolismus   MeSH
• mikroskopie MeSH
• mitogenem aktivované proteinkinasy * metabolismus   MeSH
• rostliny metabolismus   MeSH
• Sinorhizobium meliloti * metabolismus   MeSH
• symbióza fyziologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• mitogenem aktivované proteinkinasy * MeSH

The mitogen-activated protein kinase (MAPK) family is highly conserved in mammals, and is involved in a variety of physiological phenomena like regeneration, development, cell proliferation, and differentiation. In this study, 13 MAPK genes were identified in cattle and their corresponding protein properties were characterized using genome-wide identification and analysis. Phylogenetic analysis showed that the 13 BtMAPKs were cluster grouped into eight major evolutionary branches, which were segmented into three large subfamilies: ERK, p38 and JNK MAPK. BtMAPKs from the same subfamily had similar protein motif compositions, but considerably different exon-intron patterns. The heatmap analysis of transcriptome sequencing data showed that the expression of BtMAPKs was tissue-specific, with BtMAPK6 and BtMAPK12 highly expressed in muscle tissues. Furthermore, knockdown of BtMAPK6 and BtMAPK12 revealed that BtMAPK6 had no effect on myogenic cell proliferation, but negatively affected the differentiation of myogenic cells. In contrast, BtMAPK12 improved both the cell proliferation and differentiation. Taken together, these results provide novel insights into the functions of MAPK families in cattle, which could serve as a basis for further studies on the specific mechanisms of the genes in myogenesis.

• Klíčová slova
• Cattle, Genome-wide analysis, MAPK, Myogenesis,
• MeSH
• buněčná diferenciace genetika   MeSH
• fylogeneze MeSH
• mitogenem aktivované proteinkinasy p38 MeSH
• mitogenem aktivované proteinkinasy * metabolismus   MeSH
• multigenová rodina * MeSH
• savci MeSH
• skot genetika   MeSH
• vývoj svalů genetika   MeSH
• zvířata MeSH
• Check Tag
• skot genetika   MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mitogenem aktivované proteinkinasy p38 MeSH
• mitogenem aktivované proteinkinasy * MeSH

Oxidative stress is associated with cardiovascular and neurodegenerative diseases, diabetes, cancer, psychiatric disorders and aging. In order to counteract, eliminate and/or adapt to the sources of stress, cells possess elaborate stress-response mechanisms, which also operate at the level of regulating transcription. Interestingly, it is becoming apparent that the metabolic state of the cell and certain metabolites can directly control the epigenetic information and gene expression. In the fission yeast Schizosaccharomyces pombe, the conserved Sty1 stress-activated protein kinase cascade is the main pathway responding to most types of stresses, and regulates the transcription of hundreds of genes via the Atf1 transcription factor. Here we report that fission yeast cells defective in fatty acid synthesis (cbf11, mga2 and ACC/cut6 mutants; FAS inhibition) show increased expression of a subset of stress-response genes. This altered gene expression depends on Sty1-Atf1, the Pap1 transcription factor, and the Gcn5 and Mst1 histone acetyltransferases, is associated with increased acetylation of histone H3 at lysine 9 in the corresponding gene promoters, and results in increased cellular resistance to oxidative stress. We propose that changes in lipid metabolism can regulate the chromatin and transcription of specific stress-response genes, which in turn might help cells to maintain redox homeostasis.

• MeSH
• acetyltransferasy genetika   MeSH
• chromatin * metabolismus   MeSH
• exprese genu MeSH
• fosforylace MeSH
• metabolismus lipidů * MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• oxidační stres * MeSH
• regulace genové exprese u hub MeSH
• Schizosaccharomyces pombe - proteiny * genetika   MeSH
• Schizosaccharomyces * genetika   MeSH
• transkripční faktory bZIP genetika   MeSH
• transkripční faktory genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetyltransferasy MeSH
• Cbf11 protein, S pombe MeSH Prohlížeč
• chromatin * MeSH
• Gcn5 protein, S pombe MeSH Prohlížeč
• mitogenem aktivované proteinkinasy MeSH
• Pap1 protein, S pombe MeSH Prohlížeč
• Schizosaccharomyces pombe - proteiny * MeSH
• transkripční faktory bZIP MeSH
• transkripční faktory MeSH

Dual specificity phosphatase 7 (DUSP7) is a protein belonging to a broad group of phosphatases that can dephosphorylate phosphoserine/phosphothreonine as well as phosphotyrosine residues within the same substrate. DUSP7 has been linked to the negative regulation of mitogen activated protein kinases (MAPK), and in particular to the regulation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). MAPKs play an important role in embryonic development, where their duration, magnitude, and spatiotemporal activity must be strictly controlled by other proteins, among others by DUSPs. In this study, we focused on the effect of DUSP7 depletion on the in vitro differentiation of mouse embryonic stem (ES) cells. We showed that even though DUSP7 knock-out ES cells do retain some of their basic characteristics, when it comes to differentiation, they preferentially differentiate towards neural cells, while the formation of early cardiac mesoderm is repressed. Therefore, our data indicate that DUSP7 is necessary for the correct formation of neuroectoderm and cardiac mesoderm during the in vitro differentiation of ES cells.

• MeSH
• fosfatasa 1 s dvojí specificitou metabolismus   MeSH
• fosfatasy s dvojí specifitou genetika   metabolismus   MeSH
• fosfoserin MeSH
• fosfothreonin MeSH
• fosfotyrosin MeSH
• mezoderm metabolismus   MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• myší embryonální kmenové buňky * metabolismus   MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Dusp7 protein, mouse MeSH Prohlížeč
• fosfatasa 1 s dvojí specificitou MeSH
• fosfatasy s dvojí specifitou MeSH
• fosfoserin MeSH
• fosfothreonin MeSH
• fosfotyrosin MeSH
• mitogenem aktivované proteinkinasy MeSH

Ozone (O3) is a gaseous environmental pollutant that can enter leaves through stomatal pores and cause damage to foliage. It can induce oxidative stress through the generation of reactive oxygen species (ROS) like hydrogen peroxide (H2O2) that can actively participate in stomatal closing or opening in plants. A number of phytohormones, including abscisic acid (ABA), ethylene (ET), salicylic acid (SA), and jasmonic acid (JA) are involved in stomatal regulation in plants. The effects of ozone on these phytohormones' ability to regulate the guard cells of stomata have been little studied, however, and the goal of this paper is to explore and understand the effects of ozone on stomatal regulation through guard cell signaling by phytohormones. In this review, we updated the existing knowledge by considering several physiological mechanisms related to stomatal regulation after response to ozone. The collected information should deepen our understanding of the molecular pathways associated with response to ozone stress, in particular, how it influences stomatal regulation, mitogen-activated protein kinase (MAPK) activity, and phytohormone signaling. After summarizing the findings and noting the gaps in the literature, we present some ideas for future research on ozone stress in plants.

• Klíčová slova
• abscisic acid, ethylene, guard cells, hydrogen peroxide (H2O2), reactive oxygen species (ROS), salicylic acid,
• MeSH
• biologické modely MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• ozon farmakologie   MeSH
• průduchy rostlin účinky léků   fyziologie   MeSH
• regulátory růstu rostlin farmakologie   MeSH
• signální transdukce účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mitogenem aktivované proteinkinasy MeSH
• ozon MeSH
• regulátory růstu rostlin MeSH

Inhalation exposures to polycyclic aromatic hydrocarbons (PAHs) have been associated with various adverse health effects, including chronic lung diseases and cancer. Using human bronchial epithelial cell line HBE1, we investigated the effects of structurally different PAHs on tissue homeostatic processes, namely gap junctional intercellular communication (GJIC) and MAPKs activity. Rapid (<1 h) and sustained (up to 24 h) inhibition of GJIC was induced by low/middle molecular weight (MW) PAHs, particularly by those with a bay- or bay-like region (1- and 9-methylanthracene, fluoranthene), but also by fluorene and pyrene. In contrast, linear low MW (anthracene, 2-methylanthracene) or higher MW (chrysene) PAHs did not affect GJIC. Fluoranthene, 1- and 9-methylanthracene induced strong and sustained activation of MAPK ERK1/2, whereas MAPK p38 was activated rather nonspecifically by all tested PAHs. Low/middle MW PAHs can disrupt tissue homeostasis in human airway epithelium via structure-dependent nongenotoxic mechanisms, which can contribute to their human health hazards.

• Klíčová slova
• Gap junctional intercellular communication, Human bronchial epithelial cell line, Methylated anthracenes, Mitogen-activated protein kinases, Nongenotoxic mechanisms, Polycyclic aromatic hydrocarbons,
• MeSH
• bronchy cytologie   MeSH
• buněčné linie MeSH
• epitelové buňky účinky léků   fyziologie   MeSH
• lidé MeSH
• mezerový spoj účinky léků   MeSH
• mezibuněčná komunikace účinky léků   MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• polycyklické aromatické uhlovodíky toxicita   MeSH
• viabilita buněk účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• mitogenem aktivované proteinkinasy MeSH
• polycyklické aromatické uhlovodíky MeSH

Cytokinins are plant hormones with biological functions ranging from coordination of plant growth to the regulation of biotic and abiotic stress-related responses and senescence. The components of the plant immune system can learn from past elicitations by microbial pathogens and herbivores and adapt to new threats. It is known that plants can enter the primed state of enhanced defense induced by either natural or synthetic compounds. While the involvement of cytokinins in defense priming has been documented, no comprehensive model of their action has been provided to date. Here, we report the functional characterization of two aromatic cytokinin derivatives, 6-benzylaminopurine-9-arabinosides (BAPAs), 3-methoxy-BAPA and 3-hydroxy-BAPA, that proved to be effective in delaying senescence in detached leaves while having low interactions with the cytokinin pathway. An RNA-seq profiling study on Arabidopsis leaves treated with 3-methoxy-BAPA revealed that short and extended treatments with this compound shifted the transcriptional response markedly toward defense. Both treatments revealed upregulation of genes involved in processes associated with plant innate immunity such as cell wall remodeling and upregulation of specific MAP kinases, most importantly MPK11, which is a MAPK module involved in stress-related signaling during the pathogen-associated molecular patterns (PAMPs) response. In addition, elevated levels of JA and its metabolites, jasmonate/ethylene-driven upregulation of PLANT DEFENSIN 1.2 (PDF1.2) and other defensins, and also temporarily elevated levels of reactive oxygen species marked the plant response to 3-methoxy-BAPA treatment. Synergistic interactions were observed when plants were cotreated with 3-hydroxy-BAPA and the flagellin-derived bacterial PAMP peptide (flg22), leading to the enhanced expression of the PAMP-triggered immunity (PTI) marker gene FRK1. Our data collectively show that some BAPAs can sensitively prime the PTI responses in a low micromolar range of concentrations while having no observable negative effects on the overall fitness of the plant.

• MeSH
• Arabidopsis chemie   metabolismus   MeSH
• arabinonukleosidy chemie   farmakologie   MeSH
• cytokininy chemie   farmakologie   MeSH
• imunita rostlin účinky léků   MeSH
• listy rostlin účinky léků   MeSH
• MAP kinasový signální systém účinky léků   MeSH
• mitogenem aktivované proteinkinasy genetika   metabolismus   MeSH
• molekulární struktura MeSH
• PAMP struktury farmakologie   MeSH
• proteiny huseníčku genetika   metabolismus   MeSH
• regulace genové exprese u rostlin účinky léků   MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• arabinonukleosidy MeSH
• cytokininy MeSH
• mitogenem aktivované proteinkinasy MeSH
• PAMP struktury MeSH
• proteiny huseníčku MeSH

Stomatal ontogenesis, patterning, and function are hallmarks of environmental plant adaptation, especially to conditions limiting plant growth, such as elevated temperatures and reduced water availability. The specification and distribution of a stomatal cell lineage and its terminal differentiation into guard cells require a master regulatory protein phosphorylation cascade involving the YODA mitogen-activated protein kinase kinase kinase. YODA signaling results in the activation of MITOGEN-ACTIVATED PROTEIN KINASEs (MPK3 and MPK6), which regulate transcription factors, including SPEECHLESS (SPCH). Here, we report that acute heat stress affects the phosphorylation and deactivation of SPCH and modulates stomatal density. By using complementary molecular, genetic, biochemical, and cell biology approaches, we provide solid evidence that HEAT SHOCK PROTEINS 90 (HSP90s) play a crucial role in transducing heat-stress response through the YODA cascade. Genetic studies revealed that YODA and HSP90.1 are epistatic, and they likely function linearly in the same developmental pathway regulating stomata formation. HSP90s interact with YODA, affect its cellular polarization, and modulate the phosphorylation of downstream targets, such as MPK6 and SPCH, under both normal and heat-stress conditions. Thus, HSP90-mediated specification and differentiation of the stomatal cell lineage couples stomatal development to environmental cues, providing an adaptive heat stress response mechanism in plants.

• Klíčová slova
• Arabidopsis, HSP90, MAPK, heat stress, stomata,
• MeSH
• Arabidopsis fyziologie   MeSH
• buněčná diferenciace MeSH
• buněčné dělení MeSH
• buněčný rodokmen MeSH
• epigeneze genetická MeSH
• fosforylace MeSH
• kotyledon cytologie   MeSH
• MAP kinasy kinas (kinas) genetika   metabolismus   MeSH
• mitogenem aktivované proteinkinasy kinas metabolismus   MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• mutace MeSH
• proteiny huseníčku genetika   metabolismus   MeSH
• proteiny tepelného šoku HSP90 genetika   metabolismus   MeSH
• průduchy rostlin cytologie   růst a vývoj   metabolismus   MeSH
• reakce na tepelný šok * MeSH
• regulace genové exprese u rostlin MeSH
• signální transdukce MeSH
• transkripční faktory bHLH metabolismus   MeSH
• vazba proteinů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• AtMPK3 protein, Arabidopsis MeSH Prohlížeč
• MAP kinasy kinas (kinas) MeSH
• mitogenem aktivované proteinkinasy kinas MeSH
• mitogenem aktivované proteinkinasy MeSH
• MPK6 protein, Arabidopsis MeSH Prohlížeč
• proteiny huseníčku MeSH
• proteiny tepelného šoku HSP90 MeSH
• SPEECHLESS protein, Arabidopsis MeSH Prohlížeč
• transkripční faktory bHLH MeSH
• YODA protein, Arabidopsis MeSH Prohlížeč

BACKGROUND: Dual inhibition of the mitogen-activated protein kinase pathway with BRAF/MEK inhibitor (BRAFi/MEKi) therapy is a standard treatment for BRAFV600-mutant metastatic melanoma and has historically been associated with grade III pyrexia or photosensitivity depending on the combination used. The objective of this study was to fully describe adverse events from the COLUMBUS study evaluating the most recent BRAF/MEK inhibitor combination encorafenib+binimetinib. PATIENTS AND METHODS: Patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma were randomised to receive encorafenib 450 mg once daily plus binimetinib 45 mg twice daily, encorafenib 300 mg once daily or vemurafenib 960 mg twice daily. Adverse events that represent known effects of available BRAFi and/or MEKi were evaluated. RESULTS: The safety population included a total of 570 patients (encorafenib+binimetinib = 192; encorafenib = 192; vemurafenib = 186). Median duration of exposure was longer with encorafenib+binimetinib (51 weeks) than with encorafenib (31 weeks) or vemurafenib (27 weeks). Common BRAFi/MEKi toxicities with encorafenib+binimetinib were generally manageable, reversible and infrequently associated with discontinuation. Pyrexia was less frequent with encorafenib+binimetinib (18%) and encorafenib (16%) than with vemurafenib (30%) and occurred later in the course of therapy with encorafenib+binimetinib (median time to first onset: 85 days versus 2.5 days and 19 days, respectively). The incidence of photosensitivity was lower with encorafenib+binimetinib (5%) and encorafenib (4%) than with vemurafenib (30%). The incidence of serous retinopathy was higher with encorafenib+binimetinib (20%) than with encorafenib (2%) or vemurafenib (2%), but no patients discontinued encorafenib+binimetinib because of this event. CONCLUSION: Encorafenib+binimetinib is generally well tolerated and has a low discontinuation rate in patients with BRAFV600-mutant melanoma, with a distinct safety profile as compared with other anti-BRAF/MEK targeted therapies. TRIAL REGISTRATION: ClinicalTrials.gov (Identifier: NCT01909453) and with EudraCT (number 2013-001176-38).

• Klíčová slova
• Binimetinib, Encorafenib, Melanoma, Safety, Vemurafenib,
• MeSH
• benzimidazoly aplikace a dávkování   škodlivé účinky   MeSH
• incidence MeSH
• inhibitory proteinkinas aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• karbamáty aplikace a dávkování   škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• melanom farmakoterapie   genetika   metabolismus   MeSH
• mitogenem aktivované proteinkinasy antagonisté a inhibitory   metabolismus   MeSH
• mutace MeSH
• nádory kůže farmakoterapie   genetika   metabolismus   MeSH
• nauzea chemicky indukované   epidemiologie   MeSH
• protokoly antitumorózní kombinované chemoterapie aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• protoonkogenní proteiny B-Raf antagonisté a inhibitory   genetika   metabolismus   MeSH
• sulfonamidy aplikace a dávkování   škodlivé účinky   MeSH
• únava chemicky indukované   epidemiologie   MeSH
• vemurafenib aplikace a dávkování   škodlivé účinky   MeSH
• zvracení chemicky indukované   epidemiologie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze III MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Názvy látek
• benzimidazoly MeSH
• binimetinib MeSH Prohlížeč
• encorafenib MeSH Prohlížeč
• inhibitory proteinkinas MeSH
• karbamáty MeSH
• mitogenem aktivované proteinkinasy MeSH
• protoonkogenní proteiny B-Raf MeSH
• sulfonamidy MeSH
• vemurafenib MeSH