Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.2 (guanylate cyclase)
 8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We earlier showed that the diacylglycerol (DG) lipase inhibitor, RHC 80267, increased the steady-state level of DG and inhibited the release of arachidonic acid (AA) in carbamylcholine (CCh)-stimulated pancreatic minilobules (J. F. Dixon and L. E. Hokin, (1984) J. Biol. Chem. 259, 14418-14425). There was no effect on phospholipid metabolism. We have now investigated the effect of RHC 80267 on CCh-stimulated formation of inositol monophosphate formation, cGMP formation, and amylase release. CCh (10 microM) increased cGMP formation by approximately 20-fold, and this response was inhibited 55-75% by RHC 80267 (75-100 microM). RHC 80267 had no effect on either nitroprusside- or calcium ionophore-stimulated cGMP formation, arguing against a direct inhibition of guanylate cyclase by RHC 80267. Arachidonic acid, the release of which is inhibited by RHC 80267, neither stimulated cGMP formation nor reversed the effect of RHC 80267 on CCh-stimulated cGMP formation. This suggests, but does not prove, that the rise in cGMP in response to CCh is not due to an increase in AA as has been suggested. Both phorbol myristate acetate (25 nM) and the DG kinase inhibitor R 59022 (10 microM) inhibited CCh-stimulated cGMP formation by 40%. RHC 80267 also inhibited CCh-stimulated inositol phosphate accumulation and amylase release by 60 and 40%, respectively. The data suggest that the inhibition of CCh-stimulated cGMP formation and other muscarinic responses by RHC 80267 is probably the result of feedback inhibition of the cholinergic receptor via activation of protein kinase C by the elevated DG.
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PMID:Inhibitors of diacylglycerol lipase and diacylglycerol kinase inhibit carbamylcholine-stimulated responses in guinea pig pancreatic minilobules. 244 62

The biochemical events initiated by mitogen in T lymphocytes are the subject of this paper. Following interaction of the mitogen with its receptors, a transmembrane 'trigger-type' signal is propagated which has both positive and negative correlates. The negative signal occurs with high mitogen concentrations and is associated with membrane freezing, microtubular aggregation, receptor capping, adenylate cyclase activation, and cellular cyclic AMP increases. The positive signal occurs with optimal mitogen concentrations and is associated with changes in membrane permeability and transport with influx of calcium and potassium ion and efflux of sodium, in transport processes for glucose, amino acids, and nucleosides, and in a collected series of early membrane lipid changes which can be considered essential for the positive signal. These lipid changes include the uptake of arachidonic acid and other fatty acids, choline, phosphate and other molecules, their incorporation into membrane phospholipids, particularly phosphatidylinositol (PI), and a turnover of PI with the production of inositol triphosphate, which can be related to calcium mobilization and diacylglycerol which activates a cytoplasmic protein kinase C. A key event associated with mitogen action is arachidonic acid release. Arachidonic acid may give rise to prostaglandins and thromboxanes as part of negative components of the signal through effects on the adenylate cyclase/cyclic AMP system. Arachidonic acid gives rise to eicosanoids like 5-, 11-, possibly 12- and 15-hydroxyperoxy and hydroxy eicosatetraenoic acids and leukotrienes B4 and C4. The activation of the 5-lipoxygenase, a critical calcium-dependent step, leads via the production of 5-HPETE and 5-HETE to the activation of membrane and soluble guanylate cyclase and the production of cyclic GMP. Cyclic GMP appears to be essential for mitogen activation and is associated with cyclic GMP-dependent protein kinase activation and the phosphorylation of a number of substrates. Calcium ion influx is clearly central to mitogen action. Calcium through its influx and mobilization from cellular stores is thought to contribute directly and indirectly through the action of calmodulin and protein kinase C to the activation of a number of enzymatic processes involved in the positive signal including phospholipase C, diglyceride kinase and lipase, 5-lipoxygenase, and guanylate cyclase. Cyclic GMP and calcium ion both participate in nuclear processes leading to RNA and protein synthesis. Interleukin 2 is associated with midcycle increases in cyclic GMP and entry into DNA synthesis.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Transduction of signals in the activation of T lymphocytes: relation to leukemia. 304 Mar 20

Toxoplasma gondii establishes a lifelong chronic infection in humans and animals1. Host cell entry and egress are key steps in the lytic cycle of this obligate intracellular parasite, ensuring its survival and dissemination. Egress is temporally orchestrated, underpinned by the exocytosis of secretory organelles called micronemes. At any point during intracellular replication, deleterious environmental changes such as the loss of host cell integrity can trigger egress2 through the activation of the cyclic guanosine monophosphate-dependent protein kinase G3. Notably, even in the absence of extrinsic signals, the parasites egress from infected cells in a coordinated manner after five to six cycles of endodyogeny multiplication. Here we show that diacylglycerol kinase 2 is secreted into the parasitophorous vacuole, where it produces phosphatidic acid. Phosphatidic acid acts as an intrinsic signal that elicits natural egress upstream of an atypical guanylate cyclase (GC), which is uniquely conserved in alveolates4 and ciliates5, and composed of a P4-ATPase and two GC catalytic domains. Assembly of GC at the plasma membrane depends on two associated cofactors - the cell division control 50.1 and a unique GC organizer. This study reveals the existence of a signalling platform that responds to an intrinsic lipid mediator and extrinsic signals to control programmed and induced egress.
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PMID:Phosphatidic acid governs natural egress in Toxoplasma gondii via a guanylate cyclase receptor platform. 3094 49

This study sought novel ionizing radiation-response (IR-response) genes in Caenorhabditis elegans (C. elegans). C. elegans was divided into three groups and exposed to different high doses of IR: 0 gray (Gy), 200 Gy, and 400 Gy. Total RNA was extracted from each group and sequenced. When the transcriptomes were compared among these groups, many genes were shown to be differentially expressed, and these genes were significantly enriched in IR-related biological processes and pathways, including gene ontology (GO) terms related to cellular behaviours, cellular growth and purine metabolism and kyoto encyclopedia of genes and genomes (KEGG) pathways related to ATP binding, GTPase regulator activity, and RNA degradation. Quantitative reverse-transcription PCR (qRT-PCR) confirmed that these genes displayed differential expression across the treatments. Further gene network analysis showed a cluster of novel gene families, such as the guanylate cyclase (GCY), Sm-like protein (LSM), diacylglycerol kinase (DGK), skp1-related protein (SKR), and glutathione S-transferase (GST) gene families which were upregulated. Thus, these genes likely play important roles in IR response. Meanwhile, some important genes that are well known to be involved in key signalling pathways, such as phosphoinositide-specific phospholipase C-3 (PLC-3), phosphatidylinositol 3-kinase age-1 (AGE-1), Raf homolog serine/threonine-protein kinase (LIN-45) and protein cbp-1 (CBP-1), also showed differential expression during IR response, suggesting that IR response might perturb these key signalling pathways. Our study revealed a series of novel IR-response genes in Caenorhabditis elegans that might act as regulators of IR response and represent promising markers of IR exposure.
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PMID:High-throughput transcriptome sequencing reveals extremely high doses of ionizing radiation-response genes in Caenorhabditis elegans. 3158 52