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

---

Query: EC:3.1.3.16 (calcineurin)
17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The main regulators of aldosterone secretion in adrenal gland zona glomerulosa (ZG) cells are the hormones angiotensin II (Ang II) and adrenocorticotrophin (ACTH) and small increases in the extracellular potassium (K(+)) concentration. The action of these agonists is mediated by different signalling systems - ACTH is mediated by cAMP and activation of protein kinase A while Ang II and K(+) activate two protein kinases, Ca(2+)-calmodulin-dependent protein kinase (CamK) and diacylglycerol-dependent protein kinase (PKC). Ang II, besides being one of the main agonists for the secretion of aldosterone, also stimulates proliferation of ZG cells, a process mediated by mitogen-activated protein kinases (MAPKs). Recent studies aimed at elucidating the molecular mechanisms underlying cell proliferation have shown that calcineurin is the principal regulator of MAPKs activity. The purpose of this review is to discuss experimental evidence of possible reciprocal influences between the signalling pathways regulating proliferation and steroidogenesis in ZG cells.
...
PMID:Reciprocal influences between the signalling pathways regulating proliferation and steroidogenesis in adrenal glomerulosa cells. 1517 20

The effects of authentic nitric oxide (NO, 10(-6) M) and NO-donors such as sodium nitroprusside (SNP, 10(-5) M) and glyceryl trinitrate (GTN, 10(-4) M) on contractile force and free intracellular calcium level ([Ca2+]i) were studied on precontracted with high potassium chloride (KCl, 70 mM) isolated rings of rat tail artery. The sensitivity of contractile myofilaments to Ca2+ was measured using chemically permeabilized (alpha-toxin, beta-escin, Triton X-100) vascular rings. [Ca2+]i and contractile activity were measured simultaneously. The relationship of [Ca2+]i and tension developed was studied in endothelium-denuded rings and controlled calcium response was evaluated in both endothelium-denuded and permeabilized vascular rings. Both authentic NO and NO-donors decreased [Ca2+]i and high potassium-induced tension with a different time course. Inhibitor of soluble guanylyl cyclase (sGC) LY83583 (10(-5) M) did not affect SNP-induced relaxation whereas the other sGC inhibitor ODQ (10(-6) M) attenuated SNP-induced relaxation. Both inhibitors had no effect on NO- and SNP-induced reduction in [Ca2+]i. On the contrary, GTN induced neither relaxation nor decrease in [Ca2+]i on application of both LY83583 and ODQ. Tail artery rings permeabilized with alpha-toxin, beta-escin, but not with Triton X-100 were relaxed by authentic NO and NO-donors, but to a less extent than non-permeabilized rings. Dithioerythritol (DTE, 5 x 10(-3) M) that maintains sulfhydryl (SH) groups in reduced state preventing their nitrosylation attenuated NO-induced relaxation in both non-permeabilized and permeabilized tail artery rings. The cyclic heptapeptide mycrocystin-LR (MC-LR) (10(-5) M), an inhibitor of type 1 and 2A phosphatases, induced sustained increase in tension of beta-escin permeabilized rings in low Ca2+ (10(-8) M) solution. The tension was not affected by authentic NO and SNP. We conclude that authentic NO and SNP relax rat tail artery smooth muscle (SM) in the presence of inhibitors of sGC via cyclic guanosine monophosphate (cGMP)-independent pathway, whereas relaxation induced by GTN is inhibited. The data demonstrate that cGMP-dependent pathway in vascular smooth muscle is ubiquitous, but not the only way of relaxation induced by NO. NO can modulate vascular tone directly by reducing sensitivity of contractile myofilaments to [Ca2+]i and may involve activation of protein phosphatase(s).
...
PMID:Nitric oxide relaxes rat tail artery smooth muscle by cyclic GMP-independent decrease in calcium sensitivity of myofilaments. 1519 64

GHRH plays a pivotal role in the regulation of both synthesis and secretion of GH in the anterior pituitary. In this study, we examined the molecular mechanism of depolarization-induced GHRH gene transcription using the hypothalamus cell line, Gsh+/+, revealing the involvement of the transcription factor called nuclear factor of activated T cells (NFAT). GHRH, NFAT1, NFAT4, and related genes were endogenously expressed in Gsh+/+ cells and the rat arcuate nucleus, where NFAT1 and GHRH were colocalized. Cellular excitation with high potassium potently stimulated endogenous GHRH gene 5'-promoter activity as well as the NFAT-mediated gene transcription, the former being further enhanced by coexpression of NFAT. On the other hand, cyclosporin A (a calcineurin-NFAT inhibitor) or EGTA (a calcium chelator) significantly blocked the depolarization-induced GHRH gene transcription. EMSA and site-directed mutagenesis experiments showed the direct binding of NFAT at five sites of the GHRH promoter, among which the relative importance of three distal sites (-417/-403, -402/-387, -317/-301) was suggested. Finally, elimination of all five sites completely abolished the NFAT-induced GHRH gene up-regulation. Altogether, our results suggest that the transcription factor NFAT is involved in the depolarization-induced transcriptional activation of GHRH gene in the neuronal cells.
...
PMID:Nuclear factor of activated T cells (NFAT) is involved in the depolarization-induced activation of growth hormone-releasing hormone gene transcription in vitro. 1531 55

We showed previously that exposure to microcystin-LR causes renal toxic effects in isolated perfused rat kidney, and that inflammatory mediators from supernatants of macrophages stimulated by microcystin-LR are involved in this process. The aim of this research was to examine water and electrolytes secretion in vivo, induced by microcystin-LR and supernatant of macrophages stimulated for this toxin (SUP.MphiS + MCLR), using perfused rat ileal segment and ligated intestinal loop models. We found microcystin-LR at 1 microg/ml (0.09 +/- 0.003* vs. control 0.07 +/- 0.001 g of secretion/2 cm of loop; P < 0.05*) and the SUP.MphiS + MCLR after 18 h postinoculation (0.10 +/- 0.003 vs. control 0.03 +/- 0.002 g/cm) caused intestinal secretion. In addition, microcystin-LR caused significant sodium secretion (-2.18 +/- 0.72* vs. control 2.18 +/- 0.50 microEq g(-1) min(-1)), potassium (-0.26 +/- 0.04* vs. control 0.32 +/- 0.03 microEq g(-1) min(-1)), chloride (MCLR = -3.29 +/- 1.93* vs. control 0.88 +/- 1.25 microEq g(-1) min(-1)) and water (-0.012 +/- 0.004* vs. control 0.002 +/- 0.002 ml g(-1) min(-1)). We also demonstrated SUP.MphiS + MCLR to induce intestinal secretion of electrolytes (sodium, potassium, chloride) and water. These findings suggested that microcystin-LR and lamina propria macrophages-derived mediators are able to induce intestinal secretion in vivo, probably via inhibition of protein phosphatase.
...
PMID:Microcystin-LR promote intestinal secretion of water and electrolytes in rats. 1545 Sep 31

The potassium channel KCNQ4, expressed in the mammalian cochlea, has been associated tentatively with an outer hair cell (OHC) potassium current, I(K,n), a current distinguished by an activation curve shifted to exceptionally negative potentials. Using CHO cells as a mammalian expression system, we have examined the properties of KCNQ4 channels under different phosphorylation conditions. The expressed current showed the typical KCNQ4 voltage-dependence, with a voltage for half-maximal activation (V(1/2)) of -25 mV, and was blocked almost completely by 200 microM linopirdine. Application of 8-bromo-cAMP or the catalytic sub-unit of PKA shifted V(1/2) by approximately -10 and -20 mV, respectively. Co-expression of KCNQ4 and prestin, the OHC motor protein, altered the voltage activation by a further -15 mV. Currents recorded with less than 1 nM Ca(2+) in the pipette ran down slowly (12% over 5 min). Buffering the pipette Ca(2+) to 100 nM increased the run-down rate sevenfold. Exogenous PKA in the pipette prevented the effect of elevated [Ca(2+)](i) on run-down. Inhibition of the calcium binding proteins calmodulin or calcineurin by W-7 or cyclosporin A, respectively, also prevented the calcium-dependent rapid run-down. We suggest that KCNQ4 phosphorylation via PKA and coupling to a complex that may include prestin can lead to the negative activation and the negative resting potential found in adult OHCs.
...
PMID:Regulation of the voltage-gated potassium channel KCNQ4 in the auditory pathway. 1566 Feb 59

Regulation of the heart by the sympathetic nervous system, fundamental to the physiological response to stress and exercise, requires coordinated phosphorylation of multiple downstream molecular targets, including the I(Ks) (slowly activating potassium current) channel. Sympathetic nervous system stimulation increases intracellular cAMP for which targeted regulation is directed in large part by distinct scaffold or anchoring proteins. Yotiao is an A-kinase-anchoring protein (AKAP) that recruits the cyclic AMP-dependent protein kinase (protein kinase A (PKA)) and protein phosphatase 1 to the carboxyl terminus of the I(Ks) channel to form a molecular complex and control its phosphorylation state, crucial to the cardiac cellular response to sympathetic nervous system stimulation. Here we report that Yotiao itself is a substrate for PKA phosphorylation, and we identify a Yotiao amino-terminal (N-T) residue (Ser-43) that is PKA-phosphorylated in response to beta-adrenergic receptor stimulation. The replacement of Ser-43 by Ala ablates the PKA phosphorylation of N-T Yotiao and markedly diminishes the functional response of the wild type and pseudo-phosphorylated I(Ks) channel to cAMP but neither prevents the PKA phosphorylation of KCNQ1 nor its binding to Yotiao. These results suggest, for the first time, a critical role for the PKA phosphorylation of an AKAP in the functional regulation of an ion channel protein and postphosphorylation allosteric modulation of the I(Ks) channel by Yotiao.
...
PMID:Phosphorylation of the A-kinase-anchoring protein Yotiao contributes to protein kinase A regulation of a heart potassium channel. 1600 9

In dissociated cultures of cerebellar granule cells, extracellular high potassium (HK) and low potassium (LK) concentrations control cell survival and apoptosis, respectively. Apoptosis-associated tyrosine kinase (AATYK) is up-regulated during the LK-induced apoptosis. Overexpression of wild-type AATYK, but not its kinase-deficient mutant, stimulates apoptosis in LK. In this study, we analyzed the relationship between the phosphorylation states of AATYK and the survival of granule cells. AATYK was hypophosphorylated in HK, whereas it was hyperphosphorylated in apoptotic LK. HK-dependent hypophosphorylation of AATYK was controlled by L-type voltage-dependent calcium channel-mediated Ca2+ influx followed by Ca2+-dependent protein phosphatase activity. However, LK-induced hyperphosphorylation of AATYK at multiple sites was blocked by kainate, lithium, and protein kinase C-delta inhibitor. AATYK phosphorylation was concurrent with c-Jun phosphorylation. In addition, mutations of AATYK on either the kinase domain or Ser-480, Ser-558, and Ser-566 residues suppressed the LK-induced hyperphosphorylation and apoptosis, suggesting the involvement of self-kinase activity and these Ser residues in this process. Our data therefore indicate that the phosphorylation states of AATYK are closely related to the HK-induced survival and LK-induced apoptosis of cerebellar granule cells.
...
PMID:Apoptosis-associated tyrosine kinase (AATYK) has differential Ca2+-dependent phosphorylation states in response to survival and apoptotic conditions in cerebellar granule cells. 1610 Mar 93

TWIK-related spinal cord K+ channel (TRESK) is the most recently cloned two-pore-domain potassium (2PK+) channel, regulated by the calcium/calmodulin-dependent protein phosphatase calcineurin. Functional identification of endogenous TRESK and its distinction from the other 2PK+ channels, producing similar background K+ current, are impeded by the lack of specific inhibitors. Therefore, we searched for antagonists selective against TRESK among the mouse 2PK+ channels by screening more than 200 substances. Mibefradil, zinc, and mercuric ions inhibited TRESK expressed in Xenopus laevis oocytes with IC50 values lower than 10 microM. The specificity of the identified agents was determined by measuring their effects on mouse TALK-1, TASK-1, TASK-2, TASK-3, THIK-1, TRAAK, TREK-1, and TREK-2. Mibefradil failed to discriminate well among the functional 2PK+ channels; however, Zn2+ and Hg2+ exerted a significantly stronger inhibitory effect on TRESK than on the other channels. Sensitivity to zinc but insensitivity to ruthenium red were distinctive features of TRESK. Whereas both Zn2+ and Hg2+ were selective blockers of TRESK among the mouse 2PK+ channels, human TRESK was resistant to Zn2+; it was blocked only by Hg2+. His132 of mouse TRESK was partly responsible for this difference. Mouse TRESK expressed in COS-7 cells was also inhibited by Zn2+ and Hg2+, and TRESK single-channel current was diminished in outside-out patches, indicating that the action of the ions was membrane-delimited, most probably targeting the channel itself. Thus, both Zn2+ and Hg2+ are expected to inhibit endogenous TRESK in isolated mouse cells, and these ions can be applied to identify the calcineurin-activated 2PK+ channel in its natural environment.
...
PMID:Zinc and mercuric ions distinguish TRESK from the other two-pore-domain K+ channels. 1635 67

The slow after-hyperpolarization (sAHP) following the action potential is an important determinant of the firing patterns of enteric neurons. The channel responsible for the sAHP thus serves as a critical control point at which neurotransmitters and inflammatory mediators modulate gut motility. Many of these receptor-evoked pathways are known to inhibit the sAHP and, thus, excite enteric neurons. They act through protein kinase A (PKA) which is a strong inhibitor of the sAHP current while protein phosphatases enhance the current. Increasing evidence suggests that the sAHP is mediated by the opening of intermediate-conductance Ca-activated potassium (IK) channels. This neuronal IK channel, previously known to be expressed in a variety of non-excitable cells, is strongly influenced by protein kinases. Investigation of the molecular basis for the modulation of IK channels by protein phosphorylation indicates that there are multiple mechanisms of channel control. Inhibition of channel activity by PKA involves phosphorylation sites located within the calmodulin-binding domain of the channel. The localization of these sites within the region involved in Ca2+ activation suggests that PKA-mediated phosphorylation of the channel opposes the conformational changes caused by binding of Ca/calmodulin, which would otherwise lead to opening of the channel. We suggest that the channel exists as a macromolecular complex involving calmodulin, protein kinases, protein phosphatase and possibly other proteins. The regulation of the channel through kinases and phophatases results in exquisite control of neuronal firing and subsequent modulation of enteric reflexes.
...
PMID:Regulation of the slow afterhyperpolarization in enteric neurons by protein kinase A. 1664 6

The ability of Bacillus subtilis to form spores is a strategy for survival under unfavorable environmental conditions. It is equally crucial to break spore dormancy and return to vegetative growth at the appropriate time. Here we present data showing that the PrpE phosphatase is involved in the control of expression of genes coding for GerA receptors, which are necessary for L-alanine-induced spore germination. Moreover, PrpE is also involved in aspartic acid, glucose, fructose, and potassium (AGFK)-induced spore germination by controlling expression of genes coding for GerK receptors. In the absence of PrpE, the production of spores was essentially normal. However, L-alanine-induced spore germination and, to a lesser extent, the AGFK-induced pathway were abolished. In contrast, the germination pathway dependent on Ca2+-dipicolinate or dodecylamine remained intact. A protein phosphatase PrpE-green fluorescent protein fusion was localized to the prespore and to the dormant spore, consistent with a role in controlling expression of genes coding for GerA receptors. We propose that PrpE is an important element in a signal transduction pathway in Bacillus subtilis that controls the expression of genes coding for germination receptors.
...
PMID:Expression of genes coding for GerA and GerK spore germination receptors is dependent on the protein phosphatase PrpE. 1674 Sep 44


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---