Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glycogen synthase kinase 3 (GSK3) regulates cellular metabolism and cell cycle via different signalling pathways. In response to insulin and growth factors GSK3 is serine-phosphorylated and inactivated. We analysed GSK3B expression and activation in bovine cumulus cells (CC) and oocytes at different meiotic stages in vitro in parallel with MAP kinases ERK (MAPK3/MAPK1) and p38 (MAPK14). GSK3B localised to cytoplasm in granulosa cells and in oocytes throughout folliculogenesis. In mature metaphase-II (MII) oocytes, GSK3B was concentrated to the region of midzone between the oocyte and the first polar body, as well as active phospho-Thr Aurora A kinase (AURKA). During in vitro maturation (IVM), in oocytes, phospho-Ser(9)-GSK3B level increased as well as phospho-MAPK3/MAPK1, while phospho-MAPK14 decreased. In CC, phospho-MAPK14 increased upon germinal vesicle breakdown (GVBD)/metaphase-I (MI) and then decreased during transition to MII. Administration of inhibitors of GSK3 activity (lithium chloride or 2'Z,3'E -6-bromoindirubin-3'-oxime) rapidly increased phospho-Ser(9)-GSK3B, and led to transient decrease of phospho-MAPK3/MAPK1 and to durable enhancing of phospho-MAPK14 in granulosa primary cell culture. GSK3 inhibitors during IVM diminished cumulus expansion and delayed meiotic progression. In cumulus, phospho-MAPK14 level was significantly higher in the presence of inhibitors, comparing with control, through the time of MI/MII transition. In oocytes, phospho-GSK3B was increased and phospho-MAPK3/MAPK1 was decreased before GVBD and oocytes were mainly arrested at MI. Therefore, GSK3B might regulate oocyte meiosis, notably MI/MII transition being the part of MAPK3/1 and MAPK14 pathways in oocytes and CC. GSK3B might be also involved in the local activation of AURKA that controls this transition.
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PMID:Glycogen synthase kinase 3B in bovine oocytes and granulosa cells: possible involvement in meiosis during in vitro maturation. 1947 Jul 8

In vitro maturation (IVM) of immature oocytes is widely used in assisted reproduction technologies in cattle, and is increasingly used to treat human infertility. The development competence of IVM oocytes, however, is lower than preovulatory, in vivo-matured oocytes. During maturation, cumulus cells (CC) are metabolically coupled with an oocyte and support the acquisition of its developmental potential. Our objective was to identify genes and pathways that were affected by IVM in bovine CC. Microarray transcriptomic analysis of CC enclosing in vitro- or in vivo-mature oocytes revealed 472 differentially expressed genes, including 28% related to apoptosis, correlating with twofold higher cell death after IVM than in vivo, as detected by TUNEL. Genes overexpressed after IVM were significantly enriched in functions involved in cell movement, focal adhesion, extracellular matrix function, and TGF-beta signaling, whereas under-expressed genes were enriched in regulating gene expression, energy metabolism, stress response, and MAP kinases pathway functions. Differential expression of 15 genes, including PAG11 (increased) and TXNIP (decreased), which were never detected in CC before, was validated by real-time RT-PCR. Moreover, protein quantification confirmed the lower abundance of glutathione S-transferase A1 and prostaglandin G/H synthase 2, and the higher abundance of hyaluronan synthase 2 and SMAD4, a member of TGF-beta pathway, in CC after IVM. Phosphorylation levels of SMAD2, MAPK3/1, and MAPK14, but not MAPK8, were higher after IVM that in vivo. In conclusion, IVM provokes the hyper-activation of TGF-beta and MAPK signaling components, modifies gene expression, leads to increased apoptosis in CC, and thus affects oocyte quality.
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PMID:In vitro maturation of oocytes alters gene expression and signaling pathways in bovine cumulus cells. 2328 Jun 68

Phytoalexins are small antimicrobial molecules synthesized and accumulated by plants upon exposure to pathogens. Camalexin is an indole-derived phytoalexin, which is accumulated in plants including Arabidopsis thaliana, and other Brassicaceae, which plays a major role in disease resistance against fungal pathogens. The productivity of Brassica crops is adversely affected by Alternaria blight disease, which is caused by Alternaria brassicae. In Arabidopsis thaliana, MAP kinase signalling cascade is known to be involved in synthesis of camalexin, which contributes to disease resistance against a necrtrophic fungal pathogen, Botrytis cinerea. In the present study, MAPK signalling cascade leading to biosynthesis of camalexin that triggers defense responses in B. rapa upon exposure to the most devastating nectrophic fungus, Alternaria brassicae has been elucidated with the help of previously reported MAPK cascade in Arabidopsis thaliana, Molecular modelling, docking, and protein-protein interaction analysis of MAP kinases retrieved from Brassica rapa genome have been carried out to reveal the above cascade. The tertiary structure prediction of MAPKs obtained through molecular modelling revealed that all the protein models fulfil the criteria of being the stable structures. The molecular docking of predicted models for elucidating potential partners of MAPKs revealed strong interactions between MKK1, MKK4, MKK5, MAPK3 and MAPK6 with MKK9. The MAPK signalling cascade also shows different genes that express and play major role in camalexin biosynthesis in B. rapa during defense response to A. brassicae. The understanding of MAPK defense signaling pathway in B. rapa against devastating fungal pathogen Alternaria brassicae would help in devising strategies to develop disease resistance in Brassica crops.
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PMID:Molecular modeling, docking and protein-protein interaction analysis of MAPK signalling cascade involved in Camalexin biosynthesis in Brassica rapa. 2998 84