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

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Query: EC:3.1.4.3 (phospholipase C)
18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lucifer yellow (LY) accumulation was used to measure macrophage pinocytosis. The hematopoietic growth factors, macrophage colony-stimulating factor (CSF-1), granulocyte-macrophage CSF (GM-CSF), and interleukin 3, and the macrophage activators, lipopolysaccharide and zymosan, all stimulated LY uptake in both murine bone marrow-derived macrophages (BMMs) and resident peritoneal macrophages (RPMs) without affecting LY efflux. The stimulation of pinocytosis in the poorly cycling RPMs and in BMMs by nonmitogens dissociates stimulation of pinocytosis from subsequent DNA synthesis. Regulation of pinocytosis in BMMs appears to be independent of that of urokinase-type plasminogen activator expression. The increases in CSF-mediated BMM pinocytosis were not inhibited by pertussis toxin, by elevations in intracellular cAMP, or by glucocorticoids and were only partially inhibited by inhibitors of Na+/H+ antiport and Na+/K(+)-ATPase activities. Protein kinase C activation could be involved in regulating BMM pinocytosis because phorbol myristate acetate, oleoylacyglycerol, and exogenously added phospholipase C can all stimulate it. Ca2+ ionophores were inactive, whereas the Na+/H+ ionophore monensin potently inhibited BMM pinocytosis.
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PMID:Regulation of pinocytosis in murine macrophages by colony-stimulating factors and other agents. 131 79

Purified hematopoietic growth factors such as colony-stimulating factor-1 (CSF-1) or macrophage CSF, granulocyte-macrophage CSF, and interleukin-3 or multi-CSF, stimulate the urokinase-type plasminogen activator (u-PA) activity of murine bone marrow-derived macrophages (BMM) and resident peritoneal macrophages. Granulocyte-CSF was inactive. The increases in BMM u-PA activity were inhibited by the glucocorticoid dexamethasone, and by agents that raise intracellular cyclic adenosine monophosphate levels, including prostaglandin E2 and cholera toxin. These changes in u-PA activity were paralleled by corresponding changes in u-PA mRNA levels. Evidence was obtained for protein kinase C and phospholipase C-mediated stimulation of BMM u-PA activity and mRNA levels; however, no evidence was found for an involvement of Na+/H+ exchange or Na+, K(+)-ATPase activity, Ca2+ fluxes, or pertussis toxin-sensitive G proteins. Several findings point to a dissociation between macrophage u-PA expression and DNA synthesis.
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PMID:Activation and proliferation signals in murine macrophages. Biochemical signals controlling the regulation of macrophage urokinase-type plasminogen activator activity by colony-stimulating factors and other agents. 184 64

In murine bone marrow-derived macrophages, prelabeled with either [3H]myristic acid or [3H]arachidonic acid, the mitogenic colony stimulating factors GM-CSF and IL-3 stimulated a transient increase in [3H]diacylglycerol generation. Maximum [3H]diacylglycerol levels were detected at 10-15 min. The stimulation of [3H]diacylglycerol generation was dependent on the concentration of CSF and correlated with their ability to activate a variety of processes in the macrophage, including DNA synthesis. This is the first report to demonstrate that GM-CSF elevates diacylglycerol levels in macrophages and also to show that diacylglycerol generation may be an important signaling mechanism for IL-3 action. In conjunction with our recent demonstration that the mitogenic agents CSF-1, 12-0-tetradecanoylphorbol-13-acetate and exogenous phospholipase C also stimulate diacylglycerol generation in the macrophage (Veis and Hamilton, J.Cell.Physiol., 147, 298-305, 1991), our findings suggest that an increase in diacylglycerol levels is necessary but not sufficient for macrophage proliferation.
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PMID:GM-CSF and IL-3 stimulate diacylglycerol generation in murine bone marrow-derived macrophages. 190 23

The capacity of human neutrophils (PMN) to bind tumor necrosis factor (TNF) was rapidly lost when the cells were incubated in suspension with agents that can stimulate their migratory and secretory responses. Both physiological (poly)peptides (FMLP, C5a, CSF-GM) and pharmacologic agonists (PMN, calcium ionophore A23187) induced the loss of TNF receptors (TNF-R) from the cell surface. Half-maximal loss in TNF-R ensued after only approximately 2 min with 10(-7) M FMLP at 37 degrees C, and required only 10(-9) M FMLP during a 30-min exposure. However, there were no such changes even with prolonged exposure of PMN to FMLP at 4 degrees or 16 degrees C. Scatchard analysis revealed loss of TNF-binding sites without change in their affinity (Kd approximately 0.4 nM) as measured at incompletely modulating concentrations of FMLP, C5a, PMA, or A23187. The binding of anti-TNF-R mAbs to PMN decreased in parallel, providing independent evidence for the loss of TNF-R from the cell surface. At the same time, soluble TNF-R appeared in the medium of stimulated PMN. This inference was based on the PMN- and FMLP-dependent generation of a nonsedimentable activity that could inhibit the binding of TNF to fresh human PMN or to mouse macrophages, and the ability of mAbs specific for human TNF-R to abolish inhibition by PMN-conditioned medium of binding of TNF to mouse macrophages. Soluble TNF-R activity was associated with a protein of Mr approximately 28,000 by ligand blot analysis of cell-free supernatants of FMLP-treated PMN. Thus, some portion of the FMLP-induced loss of TNF-R from human PMN is due to shedding of TNF-R. Shedding was unaffected by inhibitors of serine and thiol proteases and could not be induced with phosphatidylinositol-specific phospholipase C. Loss of TNF-R from PMN first stimulated by other agents may decrease their responsiveness to TNF. TNF-R shed by PMN may be one source of the TNF-binding proteins found in body fluids, and may blunt the actions of the cytokine on other cells.
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PMID:Shedding of tumor necrosis factor receptors by activated human neutrophils. 216 28

Murine bone marrow-derived macrophages (BMM) undergo DNA synthesis in response to growth factors such as colony stimulating factor-1 (CSF-1) and granulocyte-macrophage CSF (GM-CSF). These macrophages can also be "activated," but without subsequent DNA synthesis, by a number of other agents, including lipopolysaccharide (LPS), concanavalin A, zymosan, formyl-methionyl-leucyl-phenylalanine (FMLP), and the Ca2+ ionophore, A23187. When BMM are treated with a range of stimuli, there is some, although not perfect, correlation between transient elevations in both c-myc mRNA and c-fos mRNA levels and increases in DNA synthesis. However, enhanced DNA synthesis and oncogene expression are readily dissociated from rises in inositol phosphates and, by implication, phospholipase C-mediated hydrolysis of phosphatidyl inositol 4,5-bisphosphate. Superoxide formation in BMM can also be dissociated from the other responses and does not necessarily depend on protein kinase C activation.
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PMID:Activation and proliferation signals in murine macrophages: relationships among c-fos and c-myc expression, phosphoinositide hydrolysis, superoxide formation, and DNA synthesis. 255 11

Hepatocyte growth factor/scatter factor (HGF/SF) is a multifunctional cytokine that induces mitogenesis, motility, invasion, and morphogenesis of several epithelial and endothelial cell lines in culture. The receptor for HGF/SF has been identified as the Met tyrosine kinase. To investigate the signaling pathways that are involved in these events, we have generated chimeric receptors containing the extracellular domain of the colony-stimulating factor-1 (CSF-1) receptor fused to the transmembrane and intracellular domains of the Met receptor (MET). Madin-Darby canine kidney (MDCK) epithelial cells expressing the CSF-MET chimera dissociate and scatter in response to CSF-1. However, cells expressing a mutant CSF-MET receptor containing a phenylalanine substitution for tyrosine 1356 were unable to scatter or form branching tubules following stimulation with CSF-1. Tyrosine 1356 is essential for the recruitment of multiple substrates including the p85 subunit of PI3-kinase, phospholipase C gamma, and Grb2. In this study, we have investigated the role of PI3-kinase and a downstream target of PI3-kinase, pp70S6K, in the induction of MDCK cell scatter in response to HGF/SF. Our results demonstrate that following stimulation with HGF/SF, activation of PI3-kinase but not pp70S6K is essential for MDCK cell scatter.
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PMID:Hepatocyte growth factor-induced scatter of Madin-Darby canine kidney cells requires phosphatidylinositol 3-kinase. 749 47

The tyrosine phosphorylation responses initiated in human neutrophils by soluble and particulate agonists were characterized. Chemotactic factors, hematopoietic growth factors, and inflammatory microcrystals stimulated in a time- and concentration-dependent manner the tyrosine phosphorylation of distinct patterns of substrates: pp120, pp85, pp70, and pp60 in the case of chemotactic factors; pp155, pp130, pp120, pp85, pp60, and pp40 in the case of granulocyte macrophage-CSF; and pp130, pp120, pp70, and pp60 in the case of monosodium urate (MSU) crystals. Several of the single bands on one-dimensional blots (including pp40, pp70, and pp120) could be resolved into multiple spots on two-dimensional gels. The responses of several other chemotactic factors resembled those of FMLP. Cytokineplasts retained the capacity to respond to FMLP, granulocyte-macrophage-CSF, or MSU crystals with a stimulation of tyrosine phosphorylation, and contained the major substrates detected in intact neutrophils. Several unrelated tyrosine kinase inhibitors (herbimycin A, genistein, and erbstatin) strongly diminished the tyrosine phosphorylation response to chemotactic factors. Pertussis toxin abrogated the tyrosine phosphorylation response to FMLP, whereas protein kinase C (Ro 21-8220, chelerithryn) inhibitors were without effect. Chelation of intracellular calcium attenuated the tyrosine phosphorylation response to FMLP. These results indicate that G proteins play a crucial role in the coupling of chemotactic factor receptors to tyrosine phosphorylation and that this coupling occurs in parallel to that of phospholipase C. These results also underline the complexity of the transduction pathways implicated in the initiation of tyrosine phosphorylation.
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PMID:Tyrosine phosphorylation in activated human neutrophils. Comparison of the effects of different classes of agonists and identification of the signaling pathways involved. 751 26

Previously, it has been observed that newborn pig pial artery constriction after fluid percussion brain injury was associated with elevated CSF dynorphin and beta endorphin concentration. Additionally, brain injury reversed dynorphin-induced pial artery vasodilation to vasoconstriction. The present study was designed to characterize the relationship between opioids and activation of phospholipase C (PLC) and protein kinase C (PKC) in brain injury-induced pial vasoconstriction. Anesthetized newborn pigs equipped with a closed cranial window were connected to a percussion device consisting of a saline-filled cylindrical reservoir with a metal pendulum. Brain injury of moderate severity (1.9-2.3 atm) was produced by allowing the pendulum to strike a piston on the cylinder. Brain injury decreased pial arteriolar diameter within 10 min of injury and continued to fall progressively for 3 h (130 +/- 5, 108 +/- 4 and 102 +/- 5 microns for 0, 10 and 180 min postinjury). In contrast, the PLC inhibitor, neomycin (10(-4) M), blunted brain injury-induced pial vasoconstriction (133 +/- 4, 129 +/- 4 and 135 +/- 5 microns for 0, 10 and 180 min postinjury, respectively). Similarly, staurosporine (10(-7) M), a PKC inhibitor, also blunted brain injury-induced vasoconstriction. beta endorphin (10(-8), 10(-6) M)-induced pial artery vasoconstriction was blunted by neomycin (12 +/- 1, 19 +/- 1 vs. 2 +/- 1, 4 +/- 2% constriction before and after neomycin, respectively). Staurosporine similarly blunted beta endorphin pial constriction (10 +/- 1, 15 +/- 1 vs. 1 +/- 1, 1 +/- 1% constriction before and after staurosporine, respectively). The constrictor potential for dynorphin was also inhibited by neomycin and staurosporine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relationship between opioids and activation of phospholipase C and protein kinase C in brain injury induced pial artery vasoconstriction. 758 21

To determine the molecular basis for the transforming function of platelet-derived growth factor (PDGF)-A in NIH/3T3 cells, we have constructed chimerae consisting of the extracellular domain of the human CSF-1R (fms) linked to the cytoplasmic domain of the alpha PDGF receptor (alpha R) containing a series of deletion or point mutations. The ability of fms/alpha R chimerae to mediate CSF-1-dependent anchorage-independent growth, focus formation, and chemotaxis of NIH/3T3 cells was then examined. Our results provide evidence that a domain encompassing amino acid residues 977-1024 of the alpha PDGFR is required for ligand-dependent focus formation, but not chemotaxis or anchorage-independent growth, and that tyrosine residues within this domain constitute the major binding site for phospholipase C gamma. Therefore, our findings suggest that: (i) the focus forming function of alpha PDGFR correlates well with the ability of the receptor to bind phospholipase C gamma, and (ii) the mechanism of focus formation mediated by alpha PDGFR may be distinguished from that required for chemotaxis or anchorage-independent growth.
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PMID:Differential requirement of a motif within the carboxyl-terminal domain of alpha-platelet-derived growth factor (alpha PDGF) receptor for PDGF focus forming activity chemotaxis, or growth. 770 38

Phosphoinositide-specific phospholipase C (PLC) activities were measured in CSF from patients after subarachnoid hemorrhage (SAH). Their PLC activities were significantly higher than those in control CSF. Moreover, there was an obvious correlation between the PLC activity in CSF collected on day 3 and the preoperative clinical grade. The PLC activity was also closely correlated with the level of neuron-specific enolase as a marker of brain damage. Furthermore, the PLC activities were partially purified from CSF of patients after SAH and were immunologically identified to be PLC beta, PLC gamma, and PLC delta. These results suggest that PLCs are released into the CSF from brain tissue in conjunction with the initial hemorrhage and that their activity may reflect the extent of brain damage.
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PMID:Phospholipase C activity in cerebrospinal fluid following subarachnoid hemorrhage related to brain damage. 838 14


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