Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In mouse embryo NIH 3T3 fibroblasts, ethanol (60-80 mM) was found to enhance the stimulatory effects of sphingosine 1-phosphate (S1P) on both DNA synthesis and cell proliferation. Well-detectable potentiating effects of ethanol on S1P-induced mitogenesis required the presence of calcium (>1 mM) and zinc (20-40 microM) in the incubation medium. The amphibian tetrapeptide bombesin, which is known to mobilize intracellular calcium in fibroblasts, had no effect alone, but it approximately doubled the combined stimulatory effects of ethanol and S1P on DNA synthesis. The synergistic mitogenic effects of ethanol and S1P were also slightly enhanced, rather than inhibited, by the alcohol dehydrogenase inhibitor 4-methylpyrazole (5 mM). Of the various growth regulatory enzymes examined, ethanol detectably enhanced the stimulatory effects of S1P on the phosphosphorylation (activation) of p42/p44 mitogen-activated protein (MAP) kinases, but not of p38 MAP kinase. Cotreatment of fibroblasts with ethanol for 10 min also enhanced the stimulatory effects of S1P on the activities of c-Raf-1 kinase and p70 S6 kinase, but neither S1P nor ethanol had effects on phosphatidylinositol 3'-kinase and Akt/PKB kinase activities. Ethanol-plus-S1P-induced DNA synthesis was partially inhibited by both PD 98059 (50 microM) and rapamycin (10 nM), inhibitors of p42/p44 MAP kinase kinase and mTOR/p70 S6 kinases, respectively. The results indicate that in NIH 3T3 fibroblasts, ethanol can enhance the mitogenic effects of S1P by a zinc- and calcium-dependent mechanism involving both the rapamycin-sensitive p70 S6 kinase-dependent and the c-Raf-1/MAP kinase-dependent growth regulatory pathways.
 ...
PMID:Ethanol potentiates the mitogenic effects of sphingosine 1-phosphate by a zinc- and calcium-dependent mechanism in fibroblasts. 1033 73

The PKC1 gene in the yeast Saccharomyces cerevisiae encodes for protein kinase C which is known to control a MAP kinase cascade consisting of different kinases: Bck1, Mkk1 and Mkk2, and Mpk1. This cascade affects the cell wall integrity but the phenotype of pkc1Delta mutants suggests additional targets that have not yet been identified [Heinisch et al., Mol. Microbiol. 32 (1999) 671-680]. The pkc1Delta mutant, as opposed to other mutants in the MAP kinase cascade, displays defects in the control of carbon metabolism. One of them occurs in the derepression of SUC2 gene after exhaustion of glucose from the medium, suggesting an involvement of Pkc1p in the derepression process that is not shared by the downstream MAP kinase cascade. In this work, we demonstrate that Pkc1p is required for the increase of the activity of enzymatic systems during the derepression process. We observed that Pkc1p is involved in the derepression of invertase and alcohol dehydrogenase activities. On the other hand, it seems not to be necessary for the derepression of the enzymes of the GAL system. Our results suggest that Pkc1p is acting through the main glucose repression pathway, since introduction of an additional mutation in the PKC1 gene in yeast strains already presenting mutations in the HXKII or MIG1 genes does not interfere with the typical derepressed phenotype observed in these single mutants. Moreover, our data indicate that Pkc1p participates in this process through the control of the cellular localization of the Mig1 transcriptional factor.
 ...
PMID:Relationship between protein kinase C and derepression of different enzymes. 1248 87

PYST2 is a member of a structurally homologous subfamily of MAP kinase phosphatases. A computer-based analysis of the PYST2 locus revealed that it harbors two alternative open reading frames promoted by two conserved promoter regions. Using Northern blot analysis and reverse transcription-polymerase chain reaction followed by sequencing and alignment of the products, we confirmed the existence of two mRNAs that were transcribed from this genomic region. Western blot analysis indicated that these transcripts were translated. Functional bioinformatic analysis of both transcripts revealed that exon 2 exists in only one of the PYST2 transcripts, designated PYST2-L, and has the consensus elements of the phosphatase catalytic domain (PCD). We found that the translation from the PYST2-L transcript starts 46 codons upstream from the (already-known) PYST2 5' sequence. Furthermore, the existence of three PYST2-L transcripts was indicated. These transcripts differ only in their 5' untranslated regions (5'UTRs). Unlike PYST2-L, the other mRNA (PYST2-S) is devoid of any known PCD. Analysis of the predicted Pyst2-S protein revealed the presence of the vertebrate metallothionein signature I, the mammalian defensin, and the zinc-containing alcohol dehydrogenase motifs. These motifs might confer on this protein the ability to sense changes in the cellular environment. From these and previous results, we speculate that Pyst2-S may function as a negative regulator of Pyst2-L.
 ...
PMID:Characterization of the dual-specificity phosphatase PYST2 and its transcripts. 1460 40