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)

12-O-Tetradecanoylphorbol-13-acetate (TPA) markedly enhanced the increase in L-histidine decarboxylase (HDC) activity induced by dexamethasone in mouse mastocytoma P-815 cells, even with a concentration of the latter that had the maximal effect, whereas it induced a rapid and transient increase in HDC activity, which peaked after 3 h in the absence of dexamethasone. The synergistic effect of TPA on HDC activity induced by dexamethasone was detected after 4 h, a plateau level being reached by 6 h, which was similar to the time course with dexamethasone alone. TPA enhanced the induction of HDC activity by various glucocorticoids, but had no effect on the induction by dibutyryl cAMP, prostaglandin E2 or sodium butyrate. Both 1-oleoyl-2-acetylglycerol, a protein kinase C activator, and okadaic acid, a protein phosphatase inhibitor, enhanced the increase in HDC activity induced by dexamethasone, but 4 alpha-phorbol-12,13-didecanoate, an inactive derivative of TPA, did not. Protein kinase C inhibitors, such as staurosporin, H-7 and K255a, suppressed the increase in HDC activity induced by TPA with or without dexamethasone. The enhancement of HDC activity by dexamethasone was completely suppressed by cycloheximide or actinomycin D. Furthermore, TPA markedly enhanced the accumulation of HDC mRNA due to dexamethasone (5 to 10-fold, from 6 to 12 h after). TPA did not cause a significant increase in the level of either [3H]dexamethasone binding capacity or preformed HDC activity in cells. These results taken together suggest that dexamethasone-induced de novo synthesis of HDC in mastocytoma P-815 cells is up-regulated by TPA-activated protein kinase C through the mechanism involving an increased rate of transcription.
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PMID:Synergistic effects of 12-O-tetradecanoylphorbol-13-acetate and dexamethasone on de novo synthesis of histidine decarboxylase in mouse mastocytoma P-815 cells. 131 50

Cyclic AMP-dependent protein kinase (PKA) and Ca(2+)-calmodulin dependent protein kinase II (CaMKII)-mediated phosphorylation activate histamine synthesis in nerve endings, but the phosphatases deactivating it had not been studied. In this work we show that the protein phosphatase 2A (PP2A)/protein phosphatase 1 (PP1) inhibitor okadaic acid increases histamine synthesis up to twofold in rat cortical miniprisms containing histaminergic nerve endings. This effect was mimicked by the PP2A/PP1 inhibitor calyculin, but not by the inactive analog 1-norokadaone. Other phosphatase inhibitors like endothall (PP2A), cypermethrin and cyclosporin A (protein phosphatase 2B, PP2B) had much lower effects. The effects of okadaic acid appeared to be mediated by an activation of the histamine synthesizing enzyme, histidine decarboxylase. PKA-mediated activation of histamine synthesis decreased the EC(50) and maximal effects of okadaic acid. On the other hand, CaMKII-mediated activation of histamine synthesis decreased okadaic acid maximal effects, but it increased its EC(50). In conclusion, our results indicate that brain histamine synthesis is subjected to regulation by phosphatases PP2A and PP1, and perhaps also PP2B as well as by protein kinases.
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PMID:Phosphatases regulate histamine synthesis in rat brain. 1798 4