Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Several sphingolipid derivatives, including sphingosylphosphorylcholine (SPC), regulate a multitude of biological processes. In the present study we show that both human thyroid cancer cells (FRO cells) and normal human thyroid cells express G protein-coupled receptor 4 (GPR4) and ovarian cancer G protein-coupled receptor 1 (OGR1), putative SPC-specific receptors. In FRO cells SPC evoked a concentration-dependent increase in intracellular free calcium concentration ([Ca2+]i) in a calcium containing, but not in a calcium-free buffer. Sphingosine 1-phosphate (S1P) evoked an increase in [Ca2+]i in both a calcium containing and a calcium-free buffer. The phospholipase C (PLC) inhibitor U 73122 potently attenuated the effect of SPC, suggesting that effects of SPC were mediated by a G protein coupled receptor. Overnight pretreatment of the cells with pertussis toxin did not affect the SPC-evoked response. Interestingly, SPC did not evoke an increase in inositol phosphates, although S1P did so. Furthermore, in cells pretreated with thapsigargin to deplete intracellular calcium stores, SPC still evoked an increase in [Ca2+]i, suggesting that SPC mainly evoked entry of extracellular calcium. When the cells were pretreated with the protein kinase C (PKC) inhibitor GF 109203X, or when the cells were pretreated with PMA for 24 h, the SPC-evoked calcium entry was attenuated. Thus, the SPC-evoked calcium entry was apparently dependent on PKC. In sharp contrast, the increase in [Ca2+]i evoked by S1P was not sensitive to GF 109203X. Furthermore, the calcium entry evoked by the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol was not inhibited by GF 109203X. In addition, SPC decreased the incorporation of 3H-thymidine in a concentration-dependent manner in FRO cells. Taken together, SPC may be an important factor regulating thyroid cancer cell function.
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PMID:Sphingosylphosphorylcholine enhances calcium entry in thyroid FRO cells by a mechanism dependent on protein kinase C. 1649 Mar 45

Systemic acidosis has detrimental effects on the skeleton and local acidosis is associated with bone destruction in inflammatory and neoplastic diseases. However, the mechanisms by which acidosis enhances osteoclastic bone resorption are poorly understood. Our aim was to examine the effects of acid on osteoclast survival and the involvement of cytosolic Ca(2+) in mediating these effects. Osteoclasts were isolated from long bones of newborn rats, and multinucleated osteoclast-like cells were generated from RAW 264.7 cells. Cytosolic free Ca(2+) concentration ([Ca(2+)](i)) was monitored using fura-2. Survival of rat osteoclasts over a period of 18 h was significantly enhanced by acidification of the medium from 40+/-10% at pH 7.6 to 83+/-4% at pH 7.0. Consistent with its effects on survival, acidosis suppressed osteoclast apoptosis at 6 h. We examined the possible involvement of the proton-sensing receptor ovarian cancer G protein-coupled receptor 1 (OGR1) in mediating the effects of acid. Acid-induced rise of [Ca(2+)](i) was inhibited by the OGR1 antagonist Cu(2+) and was suppressed in osteoclast-like cells in which OGR1 transcripts were depleted using RNA interference. These findings support an essential role for OGR1 in acid-induced Ca(2+) signaling in osteoclasts. Addition of Cu(2+) or chelation of cytosolic Ca(2+) with BAPTA abolished the ability of acidification to enhance osteoclast survival. Inhibition of NFAT activation with the cell-permeable peptide 11R-VIVIT did not alter the ability of acid to promote survival; however, it suppressed the increase in survival induced by RANKL. In contrast, inhibition of protein kinase C (PKC) blocked the effect of acid on osteoclast survival. Thus, this study reveals that extracellular acidification enhances osteoclast survival through an NFAT-independent, PKC-dependent pathway. Increased osteoclast survival may contribute to bone loss in systemic and local acidosis.
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PMID:Extracellular acidification enhances osteoclast survival through an NFAT-independent, protein kinase C-dependent pathway. 1796 36

Intestinal passive Mg(2+) absorption, which is vital for normal Mg(2+) homeostasis, has been shown to be regulated by luminal proton. We aimed to study the regulatory role of intestinal acid sensors in paracellular passive Mg(2+) transport. Omeprazole enhanced the expressions of acid-sensing ion channel 1a (ASIC1a), ovarian cancer G protein-coupled receptor 1 (OGR1), and transient receptor potential vanilloid 4 in Caco-2 cells. It also inhibited passive Mg(2+) transport across Caco-2 monolayers. The expression and activation of OGR1 resulted in the stimulation of passive Mg(2+) transport via phospholipase C- and protein kinase C-dependent pathways. ASIC1a activation, on the other hand, enhanced apical HCO3 (-) secretion that led, at least in part, by a Ca(2+)-dependent pathway to an inhibition of paracellular Mg(2+) absorption. Our results provided supporting evidence for the roles of OGR1 and ASIC1a in the regulation of intestinal passive Mg(2+) absorption.
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PMID:The roles of acid-sensing ion channel 1a and ovarian cancer G protein-coupled receptor 1 on passive Mg2+ transport across intestinal epithelium-like Caco-2 monolayers. 2437 28