Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using highly specific mass assays, concentrations of inositol lipids and 1,2-diacylglycerol (DAG) were determined in plasma membranes isolated from rat kidney cortex. Significantly higher concentrations of inositol lipids were determined in brush-border (BBM) than in basal-lateral (BLM) plasma membranes, although DAG concentrations were similar in both. After unilateral nephrectomy, a decrease in PtdIns(4,5)P2 and PtdIns4P, with a concomitant increase in DAG and translocation of protein kinase C (PKC), were observed in BBM but not in BLM isolated from the remaining kidney. On the other hand, stimulation of renal cortical slices with insulin-like growth factor II (IGF-II) or phenylephrine caused similar effects in BLM but not in BBM. Stimulation of phospholipase C activity with translocation of PKC only to BBM in one kidney was also induced by occlusion of blood flow through the contralateral kidney for 15 min. At 30 min after the occlusion was removed and reflow established, DAG concentration and the amount of PKC in BBM returned to control values. These results suggest that an early signal after unilateral nephrectomy is transmitted to cells through BBM and can be switched on and off by blood occlusion and reflow through the contralateral kidney, while hormonal signals caused by IGF-II and phenylephrine are transmitted to cells through BLM.
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PMID:Inositol lipid signalling occurs in brush-border membranes during initiation of compensatory renal growth in the rat. 824 Feb 63

The role of the vitamin D-induced calcium binding protein termed calbindin-D (CaBP) in the biological response to 1,25-dihydroxyvitamin D3 was assessed by photoaffinity labeling techniques. The heterobifunctional cross-linking reagent methyl-4-azidobenzoimidate was employed for studies with the 28 KD chick intestinal calbindin-D28K. Calcium-dependent interactions were evident with purified chick intestinal CaBP-immunoglobulins and bovine intestinal alkaline phosphatase; in the absence of Ca2+ there was a greatly diminished crosslinking process. There were also at least two membrane components of chick intestinal brush border membranes, with M(R) = 60,000 and 130,000, which were photoaffinity cross-linked with CaBP in a calcium-dependent manner. Similar interactions were demonstrated following incubations of CaBP with phosphatidylinositol-specific phospholipase C (PI-PLC)-treated supernatant fractions from chick intestinal brush borders. PI-PLC was shown to release 14% of the alkaline phosphatase from chick intestinal brush borders compared to greater than 80% for rabbit and chick kidney BBM preparations. Specific interactions between CaBP and brush border membrane proteins could also be demonstrated in the absence of photoaffinity labeling by Sephadex G-150 chromatography of Triton X-100 solubilized incubations between calbindin-D28K and chick intestinal BBMS, with 17% of the radiolabelled CaBP comigrating with alkaline phosphatase activity. These studies collectively demonstrate that calbindin-D28K undergoes calcium-dependent conformational changes which alter its subsequent interactions with cellular proteins in a way consistent with other calcium-binding proteins such as calmodulin or troponin C.
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PMID:Evidence for calcium mediated conformational changes in calbindin-D28K (the vitamin D-induced calcium binding protein) interactions with chick intestinal brush border membrane alkaline phosphatase as studied via photoaffinity labeling techniques. 836 39

Phospholipid signalling mediated by endothelin (ET) receptor subtypes was studied in the rat proximal tubule. In freshly isolated proximal tubule cells, ET-1, ET-2 and sarafotoxin S6c (S6c) evoked an increase in 1,2-diacylglycerol (DAG), inositol 1,4,5-trisphosphate (InsP3) and phosphocholine (PCho), suggesting stimulation of both phosphatidyl-inositol 4,5-bisphosphate- and phosphatidyl-choline-specific phospholipase C (PLC), while ET-3 increased only DAG and PCho, presumably via phosphatidyl-choline-dependent PLC. Renal cortical slices were also stimulated by the above-mentioned agonists, followed by isolation of either brush border (BBM) or basolateral (BLM) membranes for which mass measurements of inositol lipids and DAG were performed. In BBM, DAG increased in response to ET-1, ET-2 and ET-3, and was followed by protein kinase C (PKC) translocation to the BBM, while in BLM, DAG formation and translocation of PKC were observed only in response to ET-3, suggesting spatial segregation of signalling systems between two membane domains of proximal tubule cells. Tyrphostine, pertussis toxin (PTX) or cholera toxin (CTX) did not influence ET-mediated signalling in either of the membranes, suggesting involvement of PTX- and CTX-insensitive G-protein-mediated stimulation of PLCbeta by ET receptors. ET-dependent stimulation of PLC in BBM and BLM was used as a tool to examine the presence of different ET receptor subtypes in these two cell membrane domains. BQ123, an inhibitor of ETA receptors, did not prevent ET-1-mediated signalling in BBM, but an ETA,B antagonist, bosentan, inhibited ET-3-mediated signalling in BBM. In addition, an ETB agonist, S6c, stimulated PLC in BBM. Neither BQ123 nor bosentan inhibited ET-3 signalling in BLM. Therefore, these data strongly suggest the presence of ETB receptors coupled to phosphatidyl-inositol 4,5-bisphosphate- and phosphatidyl-choline-dependent PLC in BBM and ETC receptors linked to phosphatidyl-choline-dependent PLC in BLM.
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PMID:Different endothelin receptor subtypes are involved in phospholipid signalling in the proximal tubule of rat kidney. 866 90

Previous work from our laboratory demonstrated that 1,25(OH)2D3 rapidly stimulated hydrolysis of membrane polyphosphoinositides (PI) in rat colonocytes and in Caco-2 cells, generating the second messengers DAG and IP3. [Ca2+]i subsequently increased due to IP3-mediated release of intracellular Ca2+ stores, and to Ca2+ influx through a receptor-mediated Ca channel. Studies examining purified antipodal plasma membranes and experiments using Caco-2 cell monolayers found that 1,25(OH)2D3 influenced PI turnover only in the basolateral (BLM) and not brush border (BBM) membranes. Vitamin D analogues with poor affinity for the vitamin D receptor were found to effectively stimulate PI turnover, suggesting the presence of a unique vitamin D receptor in the BLM. Studies from our laboratory have demonstrated saturable, reversible binding of 1,25(OH)2 D3 to colonocyte BLM. Recently, we found that 1,25(OH)2D3 activated the tyrosine kinase c-src in colonocyte BLM by a heterotrimeric guanine nucleotide binding protein (G-protein)-dependent mechanism, with subsequent phosphorylation, translocation to the BLM, and activation of PI-specific phospholipase C gamma. Due to the rise in [Ca2+]i and DAG, two isoforms of protein kinase C (PKCalpha and PKCbeta2), but not other isoforms were activated by 1,25(OH)2D3 in rat colonocytes. Recent studies demonstrated that the seco-steroid translocated the beta2 isoform to the BLM, but not the BBM. In contrast, the alpha isoform did not translocate to either antipodal plasma membrane, but modulated IP3-mediated Ca2+ release from the endoplasmic reticulum. Preliminary studies have shown that 1,25(OH)2D3 also activated phosphatidylcholine phospholipase D (PLD) in Caco-2 cells, generating phosphatidic acid and contributing to the sustained rise in DAG. PLD stimulation occurred by both PKC-dependent and -independent mechanisms. Inhibitors of G-proteins, c-src, and PKC blunted the seco-steroid-mediated activation of PLD. Cells stably transfected with sense PKCalpha showed increased 1,25(OH)2D3-stimulated PLD activation, whereas transfectants with antisense PKCalpha had an attenuated response. In addition, 1,25(OH)2D3 also regulated PLD by activating the monomeric G-protein rho A by a mechanism independent of the G-protein/ c-src/PKC pathway.
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PMID:Rapid effects of 1,25(OH)2 vitamin D3 on signal transduction systems in colonic cells. 1032 82

In rat enterocytes, signaling through the parathyroid hormone (PTH)/PTH-related peptide receptor type 1(PTHR1) includes stimulation of adenylyl cyclase, increases of intracellular calcium, activation of phospholipase C, and the MAP kinase pathway, mechanisms that suffer alterations with ageing. The purpose of this study was to evaluate whether an alteration at the level of the PTH receptor (PTHR1) is the basis for impaired PTH signaling in aged rat enterocytes. Western Blot analysis with a specific monoclonal anti-PTHR1 antibody revealed that a 85 kDa PTH binding component, the size expected for the mature PTH/PTHrP receptor, localizes in the basolateral (BLM) and brush border (BBM) membranes of the enterocyte, being the protein expression about 7-fold higher in the BLM. Two other bands of 105 kDa (corresponding to highly glycosylated, incompletely processed receptor form) and 65 kDa (proteolytic fragment) were also seen. BLM PTHR1 protein expression significantly decreases with ageing, while no substantial decrease was observed in the BBM from old rats. PTHR1 immunoreactivity was also present in the nucleus where PTHR1 protein levels were similar in enterocytes from young and aged rats. Immunohistochemical analysis of rat duodenal sections showed localization of PTHR1 in epithelial cells all along the villus with intense staining of BBM, BLM, and cytoplasm. The nuclei of these cells were reactive to the PTHR1 antiserum, but not all cells showed the same nuclear staining. The receptor was also detected in the mucosae lamina propria cells, but was absent in globets cells from epithelia. In aged rats, PTHR1 immunoreactivity was diffused in both membranes and cytoplasm and again, PTH receptor expression was lower than in young animals, while the cell nuclei showed a similar staining pattern than in young rats. Ligand binding to PTHR1 was performed in purified BLM. rPTH(1-34) displaced [I(125)]PTH(1-34) binding to PTHR1 in a concentration-dependent fashion. In both, aged (24 months) and young (3 months) rats, binding of [I(125)]PTH was characterized by a single class of high-affinity binding sites. The affinity of the receptor for PTH was not affected by age. The maximum number of specific PTHR1 binding sites was decreased by 30% in old animals. The results of this study suggest that age-related declines in PTH regulation of signal transduction pathways in rat enterocytes may be due, in part, to the loss of hormone receptors.
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PMID:Characterization of PTH/PTHrP receptor in rat duodenum: effects of ageing. 1264 98