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)

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

Two murine monoclonal antibodies have been produced which identify a novel surface antigen expressed on human leucocytes in a non-lineage-restricted distribution. Antibodies WM-63 and WM-68 were derived after immunization of mice with human T-CLL cells and the leukaemic cell line HSB-2. Both antibodies were shown to react with over 90 per cent of normal T and B lymphocytes from peripheral blood and tonsil, and also with monocytes from peripheral blood. A subset of bone marrow leucocytes, including granulocyte-macrophage progenitors, were also reactive. No activity with non-haemopoietic cells or tissues could be identified, however WM-63 and WM-68 showed binding to virtually all cases of chronic B cell malignancy, including chronic lymphatic leukaemia and non-Hodgkin's lymphoma, as well as a proportion of cases of acute leukaemia. Although the antigen recognized by these antibodies could not be immunoprecipitated from membrane extracts, it was removed from the surface of intact cells using the proteolytic enzymes protease and papain. Re-expression on cultured cells was inhibited by incubation with puromycin, cycloheximide, and tunicamycin, indicating that the epitopes detected by WM-63 and WM-68 are likely to be carbohydrate moieties on a protein backbone. Removal of the antigen from the cell surface by treatment with the enzyme phosphatidyl-inositol phospholipase C indicates that it is linked by a phosphatidyl-inositol bond. WM-63 and WM-68 were both recently clustered at the Fourth International Workshop on Human Leucocyte Differentiation Antigens into CD-48, together with four other monoclonal antibodies. Although no biological function has been ascribed to the molecule detected by these antibodies, its restriction to the haemopoietic lineage suggests a role in regulation of leucocyte function.
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PMID:A novel non-lineage antigen on human leucocytes: characterization with two CD-48 monoclonal antibodies. 208 34

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

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

We recently described an mAb (MTS23) reactive with a membrane Ag expressed on a subset of thymic medullary stromal cells. This Ag is also constitutively expressed at high levels on peripheral B cells, macrophages, and thymic and splenic dendritic cells of C57BL/6 mice. A number of stromal cell lines derived from thymus and bone marrow also stain with MTS23, but thymocytes and peripheral T cells only weakly express the Ag detected by MTS23. Here we show that the molecule detected by MTS23 is a member of the Ly-6 family of phosphatidylinositol-anchored membrane proteins. Treatment of stromal cells with phosphatidylinositol-phospholipase C before staining completely abolished expression. Using transient expression of 293T cells and a cDNA library of a stromal cell line cloned into the pEF-BOS vector, a cDNA encoding the MTS23-target Ag was isolated. Partial sequencing and restriction enzyme mapping revealed that it represents the Ly-6A/E protein. While the physiologic significance of the presence of Ly-6 molecules on stromal cells is not clear, it has been known for some time that, at least in lymphocytes, cellular activation events can be induced upon Ly-6 engagement. We now demonstrate that Ly-6 also functions as a signal transduction molecule on stromal cells, in that granulocyte-macrophage CSF can be produced by a variety of stromal cell lines upon mAb-mediated cross-linking of Ly-6. Together with the dramatic up-regulation of Ly-6 expression on stromal cells upon IFN-gamma treatment, this is the first indication of a biologic function of an Ly-6 gene product on nonhemopoietic cells. The results suggest that Ly-6 may play a role in the cross-talk between lymphocyte precursors and stromal cells.
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PMID:Identification and functional analysis of Ly-6A/E as a thymic and bone marrow stromal antigen. 878 96

Previously, we identified peptides that stimulate phosphoinositide hydrolysis in several leukocyte cell lines from mixtures of random hexapeptide sequences. Moreover, the peptides activate phospholipase C via a pertussis toxin-sensitive G protein-coupled receptor. We now investigate the structure-activity relationship of the peptides with the goal of improving the activity of the peptides, as well as the biologic function of the peptides. Substitution of the L-methionine at the C terminus of peptides with D-methionine markedly increased the effectiveness of the peptides. The half-maximal effective concentrations of MKYMPm-NH2 and WKYMVm-NH2 for stimulation of phosphoinositide hydrolysis in U266 cells were 30 and 0.5 nM, respectively. By BIAcore analysis we confirmed the existence of a receptor for WKYMVm-NH2. Furthermore, the intracellular calcium concentration increase induced by WKYMVm-NH2 was not inhibited by several chemoattractants (FMLP, IL-8, platelet-activating factor, C5a, granulocyte-macrophage CSF, and granulocyte CSF) suggests that WKYMVm-NH2 has a unique cell surface receptor on leukocytes. WKYMVm-NH2 stimulated the phosphoinositide hydrolysis in U937, HL60, and U266 cells, as well as in human neutrophils. Moreover, WKYMVm-NH2 is more effective than FMLP in the production of superoxide in human neutrophils. The data suggest that WKYMVm-NH2 may have the ability to activate the microbicidal functions of human neutrophils.
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PMID:A peptide with unique receptor specificity: stimulation of phosphoinositide hydrolysis and induction of superoxide generation in human neutrophils. 902 31

We have tested the effect of stromal cells on the proliferation in long- and short-term cultures of primitive (Thy-1+, CD34+, CD33-, CD38- , HLA-DR , adherent in vitro and quiescent in vivo) progenitors in normal human bone marrow. These primitive cells produce granulocyte-macrophage colony-forming cells (CFU-GM) that are measured in secondary clonogenic assays. Addition of stromal cells to normal adherent haemopoietic progenitor cells reduced CFU-GM production by 80% (P =0.0002) after 1 week of incubation. In long-term culture (LTC), in the presence of stroma. the normal adherent cells did not produce significant numbers of CFU-GM until 3-4 weeks later which suggests that stromal cells reduce the probability of quiescent cell activation. This effect could not be attributed to soluble inhibitory factors and was specific to stroma grown with, rather than without, methylprednisolone. It was blocked by heparanase (H'ase) II treatment of stromal cells, by phosphatidylinositol-specific phospholipase C (PI-PLC) treatment of progenitor cells, by antibody blocking of beta1 integrin molecules or by exposure to glucose/N-acetyl-D-glucosamine/alpha-methyl-D-mannoside, but not by exposure to galactose or fructose. Moreover, these interventions enabled the progenitor cells to respond to stimulatory factors in the culture supernatant. We interpret these results as support for a model involving primitive progenitor cell binding to stroma by PI-CAM/HS, beta1 integrin activation via lectin-like interactions and the transduction of signals which reduce the ability of primitive cells to respond to ambient stimulators. This model provides a mechanism for the maintenance of the quiescent state of stem cells by adhesion to stromal cells.
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PMID:Stromal cells negatively regulate primitive haemopoietic progenitor cell activation via a phosphatidylinositol-anchored cell adhesion/signalling mechanism. 905 78