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 suppressive effect of glucocorticoids (GC) upon antigen-induced phosphatidylinositol phospholipase C (PI-PLC) activity and inositol phosphate formation by rat basophilic leukemia cells (RBL-2H3) has been characterized. Addition of antigen for a period of 1-30 min enhanced production of [3H]inositol monophosphate (IP1), inositol 1,4-bisphosphate (IP2) and inositol 1,4,5-trisphosphate (IP3) by about 5-10-fold. Pretreatment with hydrocortisone (HC) reduced formation of the various inositol phosphates (IPs) and degradation of phosphatidylinositol 4,5-bisphosphate (PIP2) by an average of 50%. Maximal inhibition of hydrolysis of PIP2 and reduction in stimulation of IP3 formation was reached after 4 h of preincubation with 2.10(-6) M of HC. Cycloheximide and RU486, a GC receptor antagonist, completely prevented the inhibitory effect of HC on IP formation. Other GC, dexamethasone (DEX) and triamcinolone (each at 2.10(-7) M) markedly suppressed antigen induced IP3 production, while aldosterone and sex steroids such as estradiol and progesterone (each at 2.10(-6) M) were virtually inactive. Antigen-stimulated phosphorylation of a 18 kDa and other proteins was inhibited by about 60% following pretreatment with the GC. This inhibition was in turn prevented by cycloheximide. DEX also doubled the activity of cellular acid phosphatase activity. The results suggest that the inhibitory effect of GC is specific, receptor-mediated, dependent on protein synthesis and possibly mediated by protein phosphatase activity.
...
PMID:Characterization of glucocorticoid inhibition of antigen-induced inositolphosphate formation by rat basophilic leukemia cells: possible involvement of phosphatases. 166 Nov 66

A study has been carried out of the effect of aldosterone on the endogenous phosphorylation and dephosphorylation of membrane-bound and of soluble proteins from toad bladder. Membrane-bound protein D (apparent molecular weight, 49,000), a protein which may possibly be involved in the regulation of sodium transport across the mucosal epithelium of toad bladder, contained a substantial fraction of the radioactive phosphate incorporated into membrane proteins; moreover, it was the only protein to appear consistently in autoradiographs of polyacrylamide gels of phosphorylated membrane proteins. Pretreatment of toad bladder slices with aldosterone caused an increase in the endogenous dephosphorylation of membrane-bound protein D. A half-maximal increase in this dephosphorylation occurred at an aldosterone concentration of 20-40 nM. The increase in protein D phosphatase activity induced by aldosterone was prevented by inhibitors of RNA and protein synthesis as well as by spironolactone, a specific antagonist of aldosterone. The mineralocorticoid, 9alpha-fluorohydrocortisone, also increased protein D phosphatase activity, but testosterone did not. Aldosterone also increased the removal of [(32)P]phosphate from protein D in the cell sap. In contrast to the increase in protein D phosphatase activity, aldosterone had little effect on the phosphorylation of protein D by endogenous protein D kinase. In some experiments, effects of aldosterone and of cAMP, qualitatively similar to those found with protein D, were also observed on the phosphorylation and dephosphorylation of a protein with an apparent molecular weight of 37,000, in both the microsomal and cell sap fractions. No consistent effect of preincubation with aldosterone or of cAMP was observed on any membrane-bound or cell sap protein other than protein D and the 37,000 dalton protein.
...
PMID:Aldosterone-induced increase in protein phosphatase activity of toad bladder. 437 94

1. A study has been made of the response of the Na efflux to injected guanosine triphosphate (GTP) in barnacle muscle fibres pre-exposed to aldosterone. 2. (i) Injection of GTP into unpoisoned fibres causes a transitory stimulation. By contrast, injection of GTP into ouabain-poisoned fibres causes a sustained stimulation. Little or no fall in Em is recorded following GTP injection. (ii) The stimulatory response to GTP of aldosterone pre-exposed ouabain-poisoned fibres differs from that seen in unexposed, ouabain-poisoned fibres, in that its magnitude is greater and always sustained. 3. The magnitude of the response to GTP depends on external Ca and pH but not external Na. The response itself is not seen at 0 degrees C. 4. (i) Verapamil reduces the size of the response to GTP only if applied before GTP. Injection of EGTA, Fe, Zn and Co partially abolishes the residual response. (ii) Injection of MgCl2 almost completely reverses the response to GTP. KCl is ineffective. 5. These results are explained by supposing that removal of internal Mg and trace elements by GTP leads to activation of phosphoprotein phosphatase.
...
PMID:Stimulation by injected guanosine triphosphate of the sodium efflux in barnacle muscle fibres pre-exposed to aldosterone. 727 33

The immunosuppressants cyclosporin A (CyA), FK-506, and rapamycin (RAP) have multiple actions on target cells that appear to be mediated by interaction of drug-binding protein complexes. Both FK-506 and CyA, but not RAP, inhibit the Ca2(+)-dependent phosphatase, calcineurin, and in so doing have been found to inhibit Na(+)-K(+)-ATPase activity in various nephron segments. Of interest, FK-506 and RAP, but not CyA, are bound by the steroid receptor-associated FK-506-binding heat shock protein of 56 kDa, HSP56. To determine the physiological effect of this interaction on a steroid-mediated phenomenon, the effect of these agents on steroid-mediated Na+ transport in A6 cells was investigated. Aldosterone stimulation of Na+ transport and Na(+)-K(+)-ATPase activity are significantly inhibited by prolonged incubation with FK-506 and RAP. Although CyA inhibits basal Na(+)-K(+)-ATPase activity, it has no effect on aldosterone-induced Na+ transport or the aldosterone-induced increase in Na(+)-K(+)-ATPase activity. FK-506 inhibits the aldosterone-induced synthesis of G alpha i-3 protein but has no effect on glucocorticoid receptor number as quantified by Western blotting. The results suggest that FK-506 and RAP inhibit steroid-mediated Na+ transport at some pretranslational site. The common interaction of these agents with the steroid receptor-associated HSP56 might account for these findings.
...
PMID:FK-506 and rapamycin but not cyclosporin inhibit aldosterone-stimulated sodium transport in A6 cells. 876 46

Heat shock proteins (HSP) are components of the steroid receptor complex and are released into the cell cytosol after hormone binding. We tested whether HSPs released from steroid receptors mediate an increase in calcineurin phosphatase activity by steroid hormones. Aldosterone increased calcineurin activity in microdissected rat cortical collecting ducts (CCD) and connecting tubules, but not in proximal tubules, medullary thick ascending limb, or outer medullary collecting ducts. In contrast, 5 microM dexamethasone increased calcineurin activity in both CCD and proximal tubules. Aldosterone increased CCD calcineurin activity after 30 min and this response was blocked by spironolactone, but not by actinomycin D. An antibody recognizing HSP-56 did not change basal calcineurin activity, but completely blocked the stimulation of calcineurin by aldosterone. Rapamycin, an immunosuppressive drug that stabilizes the HSP-steroid receptor complex, also blocked the aldosterone response, whereas HSP-90 or HSP-70 increased calcineurin activity in permeabilized CCD. In summary, (a) aldosterone increases calcineurin activity in CCD through a transcription-independent process; (b) maneuvers inactivating HSP-56 or slowing HSP disassociation from the receptor complex blocks stimulation of calcineurin by steroid hormones; (c) HSP-90 and HSP-70 increase CCD calcineurin activity in the absence of steroid hormone. We conclude that HSPs released from transformed steroid receptors can stimulate calcineurin activity through a transcription-independent pathway.
...
PMID:Aldosterone and dexamethasone stimulate calcineurin activity through a transcription-independent mechanism involving steroid receptor-associated heat shock proteins. 907 29

The binding of aldosterone (ALDO) to the mineralocorticoid receptor (MR) induces a conformational change of the protein referred to as 'transformation'. This feature can be evidenced in vivo by the capacity of the MR to interact with chromatin, and in vitro by the ability of the MR to bind to DNA strands or to shift the sedimentation coefficient (S) to lower values. The transformation process allows MR to work as a transcription factor after interacting with specific sequences of DNA. The signal transduction pathway for the MR transformation remains unknown. As a first step towards elucidating the mechanism of steroid-dependent MR transformation, we asked if the MR-signaling pathway is affected by the phosphorylation status of the MR-heterocomplex, and how that pathway may be regulated. Incubation of preformed [3H]ALDO-MR complex with bovine intestinal alkaline phosphatase led to an increase in the rate of MR-transformation (measured as 9.4-5.4S shift). This alkaline phosphatase-dependent MR transformation was inhibited by the specific alkaline phosphatase-type inhibitor levamisole, and was not evident in incubations performed with acid phosphatases. A direct correlation between the DNA-cellulose binding capacity of the [3H]ALDO-MR complex and the percentage of transformed 5.4S MR form was also observed. When rat kidney cytosol was incubated in the absence of both exogenous phosphatase and stabilizing agents (such as molybdate or vanadate), MR transformation also took place, in a time- and temperature-dependent process. In contrast with the inhibitory effect observed upon alkaline phosphatase-promoted transformation, levamisole was unable to inhibit the endogenous transforming activity of MR, suggesting that an endogenous phosphatase other than those which belong to the alkaline-type may be responsible for that transformation. Tautomycin, a polyketide produced by the soil bacteria Streptomyces which inhibits serine/threonine phosphatases of the PP1/PP2A subgroup, was able to inhibit the endogenous phosphatase activity in a concentration-dependent form (Ki(app)=7.35 nM). These results support the idea that the endogenous renal activity involved in the regulation of rat kidney MR transformation may be a protein phosphatase which belongs to the PP1/PP2A subgroup.
...
PMID:Tautomycin inhibits phosphatase-dependent transformation of the rat kidney mineralocorticoid receptor. 986 32

We have shown that heat shock proteins (HSPs) associated with steroid receptor complexes are involved in the activation of calcineurin by aldosterone and dexamethasone. To determine whether HSPs directly interact with calcineurin, we measured the effect of HSPs 90, 70 and 56 on calcineurin activity in a cell-free, in vitro system using a calcineurin-specific substrate. HSP-90 (75 or 100 nM) significantly increased calcineurin V(max) in the presence of calmodulin, while maximal stimulation by HSP-70 occurred at 50 nM. Bovine serum albumin (BSA) and actin did not change basal calcineurin activity indicating that HSP-90 and HSP-70 specifically activate calcineurin. Neither HSP-70, HSP-56, nor ATP augmented HSP-90-induced activation of calcineurin. In the absence of calmodulin, HSP-90 restored calcineurin activity to basal levels while higher concentrations (333 and 500 nM) increased calcineurin activity. In contrast, HSP-70 failed to activate calcineurin activity in the absence of calmodulin. Immunoprecipitation of HSP-90 from in vitro mixtures as well as protein extracts from LLCPK-1 cells demonstrates that calcineurin co-precipitates with HSP-90. In summary: (1) HSP-90 and 70 stimulate calcineurin V(max) in vitro; (2) non-specific protein interactions do not activate calcineurin activity; (3) HSP-70 and HSP-56 do not enhance HSP-90-induced activation of calcineurin; (4) HSP-70 and HSP-90 activate calcineurin via a calmodulin-dependent and independent pathways; (5) Calcineurin co-precipitates with HSP-90 from LLCPK-1 cells as well as cell-free in vitro preparations.
...
PMID:Heat shock proteins 70 and 90 increase calcineurin activity in vitro through calmodulin-dependent and independent mechanisms. 1040 16

We are used to thinking of angiotensin (Ang) II as a regulatory hormone that stimulates constriction of vascular smooth muscle cells, aldosterone release from the adrenal gland, and sodium reabsorption in the renal tubule. We have also become accustomed to understanding that Ang II may be formed and may act locally as a chemokine that induces tyrosine phosphorylation, cell growth, hypertrophy, and differentiation. Viewing Ang II as an inflammatory molecule is stranger still. Nevertheless, recent evidence shows that Ang II is important in stimulating the production of reactive oxygen species and the activation of ancient inflammatory mechanisms. The nuclear factor kappaB (NF-kappaB) is pivotal to these processes. Activation of NF-kappaB stimulates the expression of a gene menagerie that is important to chemoattraction, expression of surface adhesion molecules, coagulation, and inflammation. In addition, Ang II has been shown to regulate cellular immune responses. It stimulates the proliferation of lymphocytes and contributes to their activation via calcineurin-related pathways. Knowledge of these mechanisms may provide additional therapeutic avenues.
...
PMID:Angiotensin, inflammation, hypertension, and cardiovascular disease. 1117 10

The present study was designed to assess the effect of okadaic acid (OA), a protein phosphatase inhibitor, on aldosterone secretion in response to angiotensin II (AII), adrenocorticotropin (ACTH) and rises in external potassium concentration (K+). AII (10nM) caused a 20-fold increase in aldosterone production and OA reduced this response by 45%. ACTH (10nM) caused an 8.6-fold increase in aldosterone secretion and OA reduced this by 83%. Increasing K+ concentration from 3 to 12mM caused a 13-fold increase in aldosterone production, which OA inhibited by 36%. These results suggest that protein phosphatases participate in the control of adrenal steroid production, even though ACTH, AII and K+ act via different intracellular messenger systems.
...
PMID:Okadaic acid inhibits angiotensin II, adrenocorticotropin and potassium-dependent aldosterone secretion. 1194 18

Angiotensin II and extracellular potassium stimulate aldosterone production in adrenal glomerulosa cells by mobilizing the calcium messenger system. This response requires calcium influx across the plasma membrane, followed by calcium uptake into the mitochondria. It has been proposed that calcium is transported to the mitochondria via the lumen of the endoplasmic reticulum, acting as a kind of intracellular calcium pipeline. This hypothesis has been tested in the present study by measuring intramitochondrial calcium variations in H295R cells with a new fluorescent calcium probe, ratiometric pericam. Calyculin A, a protein phosphatase inhibitor, induced the formation of a large cortical layer of actin filaments, removing the peripheral endoplasmic reticulum away from the plasma membrane and thereby physically uncoupling the calcium channels from the pipeline. The mitochondrial calcium response to potassium was markedly reduced after calyculin treatment, but that of AngII was unaffected. Under the same conditions, potassium-stimulated pregnenolone and aldosterone production was significantly reduced, whereas the steroidogenic response to AngII remained unchanged. The inhibitory action of calyculin A on the responses to potassium was not mediated by a modification of the calcium channel activity and was not accompanied by a reduction of the cytosolic calcium response. It therefore appears that, in H295R cells, the organization of the actin cytoskeleton at the cell periphery influences the steroidogenic action of potassium, but not the response to angiotensin II. The response to potassium is proposed to be dependent on the endoplasmic reticulum-mediated transfer of calcium entering through plasma membrane calcium channels to the mitochondria.
...
PMID:Intracellular transport of calcium from plasma membrane to mitochondria in adrenal H295R cells: implication for steroidogenesis. 1296 50


1 2 3 4 5 Next >>

---