Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.12.2 (MEK)
18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

LTE1 belongs to the CDC25 family that encodes a guanine nucleotide exchange factor for GTP-binding proteins of the ras family. Previously we have shown that LTE1 is essential for termination of M phase at low temperatures. We have identified TEM1 as a gene that, when present on a multicopy plasmid, suppresses the cold-sensitive phenotype of lte1. Sequence analysis of TEM1 and GTP-binding analysis of the gene product revealed that TEM1 encodes a novel low-molecular-weight GTP-binding protein. The defect of TEM1 was lethal, and the tem1-defective cells were arrested at telophase with high H1-kinase activity under restrictive conditions, indicating that TEM1 is required to exit from M phase. The defect of TEM1 was suppressed by a high dose of CDC15, which encodes a protein kinase homologous to mitogen-activated protein kinase kinase kinases. The genetic interaction among LTE1, TEM1, and CDC15 indicates that they cooperatively play an essential role for termination of M phase.
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PMID:The yeast TEM1 gene, which encodes a GTP-binding protein, is involved in termination of M phase. 793 62

We describe here the cloning and characterization of a cDNA encoding a protein kinase that has high sequence homology to members of the mitogen-activated protein kinase (MAPK) kinase kinase (MAPKKK or MEKK) family; this cDNA is named cATMEKKI (Arabidopsis thaliana MAP kinase or ERK kinase kinase 1). The catalytic domain of the putative ATMEKK1 protein shows approximately 40% identity with the amino acid sequences of the catalytic domains of MAPKKKs (such as Byr2 from Schizosaccharomyces pombe, Ste11 from Saccharomyces cerevisiae, Bck1 from S. cerevisiae, MEKK from mouse, and NPK1 from tobacco). In yeast cells that overexpress ATMEKK1, the protein kinase replaces Ste11 in responding to mating pheromone. In this study, the expression of three protein kinases was examined by Northern blot analyses: ATMEKK1 (structurally related to MAPKKK), ATMPK3 (structurally related to MAPK), and ATPK19 (structurally related to ribosomal S6 kinase). The mRNA levels of these three protein kinases increased markedly and simultaneously in response to touch, cold, and salinity stress. These results suggest that MAP kinase cascades, which are thought to respond to a variety of extracellular signals, are regulated not only at the posttranslational level but also at the transcriptional level in plants and that MAP kinase cascades in plants may function in transducing signals in the presence of environmental stress.
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PMID:A gene encoding a mitogen-activated protein kinase kinase kinase is induced simultaneously with genes for a mitogen-activated protein kinase and an S6 ribosomal protein kinase by touch, cold, and water stress in Arabidopsis thaliana. 857 Jun 31

Brown adipose tissue hyperplasia is a fundamental response to low ambient temperature. We show here that cold exposure of an animal markedly increased the phosphorylation of mitogen-activated protein kinase (p42/p44) Erk1 and Erk2 in brown adipose tissue, and protected cells in the tissue from apoptosis. We also show that cessation of the sympathetic stimulus, by transferring cold-adapted animals to 28 degreesC, caused an increased rate of apoptosis in the tissue. In primary cultures of brown adipose tissue, norepinephrine (NE) stimulated both the phosphorylation and the activity of Erk1/2 via the Erk kinase MEK, and protected the cells form apoptosis. Similarly, agonist stimulation of alpha1- and beta-adrenergic receptors and increases in the intracellular level of Ca2+ and cAMP stimulated the phosphorylation of Erk1/2. Agonist stimulation of alpha1- and beta-adrenergic receptors, and increased intracellular cAMP level also promoted the cell survival. Furthermore, NE stimulated the expression and secretion of basic fibroblast growth factor (bFGF), which further promoted the cell survival via MEK-dependent activation of Erk1/2. In essence, we show that Erk1/2 has a critical role in promoting NE- and bFGF-dependent survival of brown adipocytes, and propose that NE- and bFGF-dependent regulation of the cell survival is involved in the cold-induced hyperplasia of brown adipose tissue.
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PMID:Ambient temperature regulation of apoptosis in brown adipose tissue. Erk1/2 promotes norepinephrine-dependent cell survival. 980 70

Various elements of the MAP kinase module have been isolated in plants. We describe here the characterisation of 14 new plant cDNAs and genes encoding putative MAP kinase kinase kinases (MAP3Ks) related to the MEKK/STE11 and RAF protein kinases. Plant MAP3Ks are characterised by a variety of primary structures conserved within closely related proteins. Southern blot analysis suggests that plant MAP3Ks are heterogenous in their genomic structure, existing either as single copy genes or as small gene families. An RT-PCR analysis showed that in Arabidopsis thaliana, all organs studied contain detectable levels of transcripts of each of the MAP3K genes identified; however, signals obtained with mature pollen were weak or non-existent except for AtMAP3Kgamma. None of the reported genes share a cell-cycle or a cold stress regulated expression.
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PMID:Characterisation of novel plant genes encoding MEKK/STE11 and RAF-related protein kinases. 1009 17

Signal transduction pathways and transcription factors are likely to be important mediators of stress responses to ischaemia and reperfusion injury following renal transplantation. We have investigated the activation of the transcription factor nuclear factor kappaB (NF-kappaB) and the mitogen activated protein kinases (MAPK), p44/42 (ERK 1/2), p38 and c-Jun N-terminal kinase (JNK) during cold stress at 4 degrees C. Human umbilical vein endothelial cells (HUVECs) were subjected to 72 h of hypothermia in a renal preservation solution. NF-kappaB activation was assessed by electromobility shift assays and MAPK activation by immunoblotting. Cell viability and apoptosis was assessed. Hypothermia activated the NF-kappaB complex, ERK 1/2 and p38 MAPK pathway. There was a 6-fold increase in NF-kappaB in the nucleus within minutes of hypothermia, correlating with p38 (p = 0.01) and ERK 1/2 activation (p = 0.03). A significant relationship was found between ERK 1/2, p38 and NF-kappaB throughout the 72 h time course (p = 0.01). In contrast, hypothermia had no effect on JNK phosphorylation. Inhibition of MAPK with an MEK inhibitor (PD098059) blocked the activation of NF-kappaB but a specific p38 inhibitor (SB203580) had no effect on NF-kappaB. Increased lactate production after 48 h indicated a switch towards anaerobic metabolism during prolonged hypothermia. Endothelial cells had a high viability and no DNA fragmentation throughout the experiment. Activation of stress pathways during organ procurement may be important in the quality of stored grafts.
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PMID:Activation of NF-kappaB and MAP kinase cascades by hypothermic stress in endothelial cells. 1215 Dec 71

In the fission yeast Schizosaccharomyces pombe the Wak1p/Win1p-Wis1p-Sty1p stress-activated protein kinase (SAPK) pathway relays environmental signals to the transcriptional machinery and modulates gene expression via a cascade of protein phosphorylation. Cells of S. pombe subjected to cold shock (transfer from 28 degrees C to 15 degrees C) transiently activated the Sty1p mitogen-activated protein kinase (MAPK) by phosphorylation. Induction of this response was completely abolished in cells disrupted in the upstream response regulator Mcs4p. The cold-triggered Sty1p activation was partially dependent on Wak1p MAPKKK and fully dependent on Wis1p MAPKK suggesting that the signal transmission follows a branched pathway, with the redundant MAPKKK Win1p as alternative transducer to Wis1p, which subsequently activates the effector Sty1p MAPK. Also, the bZIP transcription factor Atf1p became phosphorylated in a Sty1p-dependent way during the cold shock and this phosphorylation was found responsible for the increased expression of gpd1+, ctt1+, tps1+ and ntp1+ genes. Strains deleted in transcription factors Atf1p or Pcr1p were unable to grow upon incubation at low temperature whereas those disrupted in any member of the SAPK pathway were able to do so. These data reveal that S. pombe responds to cold by inducing the SAPK pathway. However, such activation is dispensable for yeast growth in cold conditions, supporting that the presence of Atf1/Pcr1 heterodimers, rather than an operative SAPK pathway, is critical to ensure yeast growth at low temperature by an as yet undefined mechanism.
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PMID:Cold induces stress-activated protein kinase-mediated response in the fission yeast Schizosaccharomyces pombe. 1238 65

Activation of the RAS/RAF/MEK/ERK/MAP kinase pathway is a known mediator of signaling that results in cellular proliferation. Moreover, this activation can lead to a growth advantage of tumor cells. Therefore, mitogenic mutations in the RAS family of oncogenes are detectable in a significant percentage in most tumors. Moreover, mutations in the BRAF gene have recently been suggested as an alternate predominant cause of colorectal and papillary thyroid cancers without ras mutations. Similar to neoplasms of other organs mutations of all three ras genes can be found in thyroid tumors. In our set of 40 cold thyroid adenoma and adenomatous nodules ras mutations were detected in only a single case. We therefore tested these hypofunctional tumors for BRAF mutations. Genomic DNA was extracted from nodular and surrounding tissue. Mutational hot spots in exons 11 and 15 of the BRAF gene were polymerase chain reaction (PCR) amplified and denaturing gradient gel electrophoresis was used to screen for mutations. No point mutation could be found in the two exons of the BRAF gene. Our study suggests that BRAF mutations are rather rare in solitary cold adenomas and adenomatous nodules and do not explain the molecular etiology of ras mutation-negative cold thyroid nodules.
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PMID:BRAF mutations are not an alternative explanation for the molecular etiology of ras-mutation negative cold thyroid nodules. 1518 12

The Arabidopsis mitogen-activated protein kinase (MAPK) kinase 2 (MKK2) and the downstream MAPKs MPK4 and MPK6 were isolated by functional complementation of osmosensitive yeast mutants. In Arabidopsis protoplasts, MKK2 was specifically activated by cold and salt stress and by the stress-induced MAPK kinase kinase MEKK1. Yeast two-hybrid, in vitro, and in vivo protein kinase assays revealed that MKK2 directly targets MPK4 and MPK6. Accordingly, plants overexpressing MKK2 exhibited constitutive MPK4 and MPK6 activity, constitutively upregulated expression of stress-induced marker genes, and increased freezing and salt tolerance. In contrast, mkk2 null plants were impaired in MPK4 and MPK6 activation and were hypersensitive to salt and cold stress. Full genome transcriptome analysis of MKK2-overexpressing plants demonstrated altered expression of 152 genes involved in transcriptional regulation, signal transduction, cellular defense, and stress metabolism. These data identify a MAP kinase signaling cascade mediating cold and salt stress tolerance in plants.
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PMID:The MKK2 pathway mediates cold and salt stress signaling in Arabidopsis. 1522 55

Salmon are subjected to hyperosmotic stress during transition from freshwater to the marine environment. A variety of mechanisms have evolved to allow movement of the animal from a hydrating to a dehydrating environment. Using differential assay of mRNA expression, a 1.3 kb transcript was found to be upregulated in branchial lamellae of salmon exposed to hyperosmotic conditions. The transcript contains an open reading frame of 618 nt coding for a 205 amino acid protein with a molecular mass of 21.5 kDa. The putative protein, dubbed salmon glycine-rich RNA binding protein (SGRP), possesses a high degree of identity (>70%) with the cold inducible RNA binding proteins (CIRP) of mammals and amphibians and contains the canonical features of these proteins including a single RNA recognition motif (RRM), high glycine content and conserved flanking motifs. SGRP mRNA was observed to increase in response to hyperosmotic stress of branchial tissue with maximum levels of expression after 48 h of exposure. Transcript also was observed in liver, kidney and heart but was not upregulated significantly by osmotic stress in these tissues. Exposure of isolated lamellae to heat stress and sodium arsenite, known inducers of hsps, did not stimulate accumulation of SGRP transcript. Similarly, inhibition of protein synthesis with cycloheximide and the MAPK and MEK signal transduction pathways with SB202190 and PD98059 failed to alter expression of the gene. Of significance was the absence of an increase in expression of SGRP in response to cold stress (DeltaT = 5 and 12 degrees C for 12 and 24 h). The findings of this research suggest that ectothermic salmon inhabiting boreal waters possess a protein analogous to the CIRPs currently identified in mammals and amphibians. In contrast to the function of CIRPs, SGRP appears to have a more prominent role in adaptation to hyperosmotic conditions rather than cold stress.
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PMID:Osmotic stress of salmon stimulates upregulation of a cold inducible RNA binding protein (CIRP) similar to that of mammals and amphibians. 1530 34

The Arabidopsis mitogen-activated protein kinase (MAPK) kinase 2 (MKK2) was shown to mediate cold and salt stress responses through activation of the two MAP kinases MPK4 and MPK6. Transcriptome analysis of plants expressing constitutively active MKK2 (MKK2-EE plants) showed altered expression of genes induced by abiotic stresses but also a significant number of genes involved in defense responses. Both MPK4 and MPK6 became rapidly activated upon Pseudomonas syringae pv. tomato DC3000 infection and MKK2-EE plants showed enhanced levels of MPK4 activation. Although MKK2-EE plants shared enhanced expression of genes encoding enzymes of ethylene (ET) and jasmonic acid (JA) synthesis, ET, JA, and salicylic acid (SA) levels did not differ dramatically from those of wild-type or mkk2-null plants under ambient growth conditions. Upon P. syringae pv. tomato DC3000 infection, however, MKK2-EE plants showed reduced increases of JA and SA levels. These results indicate that MKK2 is involved in regulating hormone levels in response to pathogens. MKK2-EE plants were more resistant to infection by P. syringae pv. tomato DC3000 and Erwinia carotovora subsp. carotovora, but showed enhanced sensitivity to the fungal necrotroph Alternaria brassicicola. Our data indicate that MKK2 plays a role in abiotic stress tolerance and plant disease resistance.
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PMID:The MAP kinase kinase MKK2 affects disease resistance in Arabidopsis. 1750 36


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