Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Yeast cells respond to a shift to higher osmolarity by increasing the cellular content of the osmolyte glycerol. This response is accompanied by a stimulation of the expression of genes encoding enzymes in the glycerol production pathway. In this study the osmotic induction of one of those genes, GPD1, which encodes glycerol-3-phosphate dehydrogenase, was monitored in time course experiments. The response is independent of the osmolyte and consists of four apparent phases: a lag phase, an initial induction phase, a feedback phase and a sustained long-term induction. Osmotic shock with progressively higher osmolyte concentrations caused a prolonged lag phase. Deletion of HOG1, which encodes the terminal protein kinase of the high osmolarity glycerol (HOG) response pathway, led to an even longer lag phase and drastically lower basal and induced GPD1 mRNA levels. However, the induction was only moderately diminished. Overstimulation of Hog1p by deletion of the genes for the protein phosphatases PTP2 and PTP3 led to higher basal and induced mRNA levels and a shorter lag phase. The protein phosphatase calcineurin, which mediates salt-induced expression of some genes, does not appear to contribute to the control of GPD1 expression. Although GPD1 expression has so far not been reported to be controlled by a general stress response mechanism, heat-shock induction of the GPD1 mRNA level was observed. However, unregulated protein kinase A activity, which strongly affects the general stress response, only marginally altered the mRNA level of GPD1. The osmotic stimulation of GPD1 expression does not seem to be mediated by derepression, since deletion of the SSN6 gene, which encodes a general repressor, did not significantly alter the induction profile. A hypoosmotic shock led to a transient 10-fold drop of the GPD1 mRNA level. Neither the HOG nor the protein kinase C pathway, which is stimulated by a decrease in external osmolarity, is involved in this effect. It was concluded that osmotic regulation of GPD1 expression is the result of an interplay between different signalling pathways, some of which remain to be identified.
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PMID:Different signalling pathways contribute to the control of GPD1 gene expression by osmotic stress in Saccharomyces cerevisiae. 1021 6

The purpose of this study was to determine whether induced expression of the Ca2+ buffering protein parvalbumin (PV) in slow-twitch fibres would lead to alterations in physiological, biochemical and molecular properties reflective of a fast fibre phenotype. Transgenic (TG) mice were generated that overexpressed PV in slow (type I) muscle fibres. In soleus muscle (SOL; 58 % type I fibres) total PV expression was 2- to 6-fold higher in TG compared to wild-type (WT) mice. Maximum twitch and tetanic tensions were similar in WT and TG but force at subtetanic frequencies (30 and 50 Hz) was reduced in TG SOL. Twitch time-to-peak tension and half-relaxation time were significantly decreased in TG SOL (time-to-peak tension: 39.3 +/- 2.6 vs. 55.1 +/- 4.7 ms; half-relaxation time: 42.1 +/- 3.5 vs. 68.1 +/- 9.6 ms, P < 0.05 for TG vs. WT, respectively; n = 8-10). There was a significant increase in expression of type IIa myosin heavy chain (MHC) and ryanodine receptor at the mRNA level in TG SOL but there were no differences in MHC expression at the protein level and thus no difference in fibre type. Whole muscle succinate dehydrogenase activity was reduced by 12 +/- 0.4 % in TG SOL and single fibre glycerol-3-phosphate dehydrogenase activity was decreased in a subset of type IIa fibres. These differences were associated with a 64 % reduction in calcineurin activity in TG SOL. These data show that overexpression of PV, resulting in decreased calcineurin activity, can alter the functional and metabolic profile of muscle and influence the expression of key marker genes in a predominantly slow-twitch muscle with minimal effects on the expression of muscle contractile proteins.
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PMID:Alterations in slow-twitch muscle phenotype in transgenic mice overexpressing the Ca2+ buffering protein parvalbumin. 1256 45

FK506 inhibits the Ca2+/calmodulin-dependent protein phosphatase calcineurin, which plays a critical role in yeast subjected to salt stress. A chemical genetic screen for small molecules that suppress growth inhibition by high NaCl plus FK506 identified a structurally related class of suppressors of FK506 (SFKs) named SFKs 2-4. To identify possible protein targets for these small molecules, a genome-wide screen of approximately 4,700 haploid yeast deletion strains was undertaken for strains showing resistance to high NaCl plus FK506. This screen yielded a number of genes not previously implicated in salt stress, including ALD6, which encodes an NADP(+)-dependent aldehyde dehydrogenase, and UTR1, which encodes an NAD+ kinase. Transcriptional profiling of yeast treated with SFK2 indicated that the SFKs target the Ald6p pathway. In addition, screening of the deletion strains for hypersensitivity to SFK2 yielded ZWF1, encoding glucose-6-phosphate dehydrogenase, which has been shown to play an overlapping role with Ald6p in NADPH production. Furthermore, the SFKs inhibited the activity of Ald6p in vitro. Having established that the SFKs target Ald6p, they were used as tools to implicate systematically other gene products in the Ald6p pathway, including Utr1p, which may function by supplying Ald6p with its NADP+ cofactor. Furthermore, growth improvement by the SFKs on high NaCl plus FK506 was shown to require GPD1, which encodes an NADH-dependent glycerol-3-phosphate dehydrogenase that is important for the production of glycerol in response to osmotic stress.
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PMID:Identification of Ald6p as the target of a class of small-molecule suppressors of FK506 and their use in network dissection. 1514 68