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)

The 47-kDa protein coimmunoprecipitated with phospholipase C (PLC)-gamma 1 by anti-PLC-gamma 1 monoclonal antibodies is proved to be Nck, a protein composed almost exclusively of one SH2 and three SH3 domains. Nck and PLC-gamma 1 are recognized by certain anti-PLC-gamma 1 monoclonal antibodies because Nck and PLC-gamma 1 share an epitope that likely is located in their SH3 domains. Nck is widely distributed in rat tissues, with an especially high level of expression in testes. The expression levels of Nck remains unchanged during the development of rat brain, whereas PLC-gamma 1 decreases during the same developmental period. Stimulation of A431 cells with epidermal growth factor elicits the tight association of Nck with the epidermal growth factor receptor and phosphorylation of Nck on both serine and tyrosine residues. The phosphorylation of Nck is also enhanced in response to stimulation of the nerve growth factor receptor in PC12 cells, the T-cell receptor complex in Jurkat cells, the membrane immunoglobulin M in Daudi cells, and the low-affinity immunoglobulin G receptor (Fc gamma RII) in U937 cells. The phosphorylation of Nck was also enhanced following treatment of A431 cells with phorbol 12-myristate 13-acetate or forskolin. These results suggest that Nck is a target for a variety of protein kinases that might modulate the postulated role of Nck as an adaptor for the physical and functional coordination of signalling proteins.
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PMID:Phosphorylation of Nck in response to a variety of receptors, phorbol myristate acetate, and cyclic AMP. 133 46

B cell activation after Ag binding to membrane Ig (mIg) is mediated by a complex series of events that involves proximal activation of a tyrosine kinase and phospholipase C. Until recently it was unclear how mIgM and mIgD, with their limited cytoplasmic domains (three amino acids on each H chain), were able to couple to these secondary signal transducers. Studies of murine B cells conducted in several laboratories, including our own, suggest that products of the mb-1 (IgM-alpha or IgD-alpha) and B29 (Ig-beta, Ig-gamma) genes occur as disulfide-linked alpha/beta and alpha/gamma heterodimers that are noncovalently associated with mIgM and mIgD. Although studies utilizing Daudi and Raji cell lines indicate that human mIgM is also associated with a dimer containing the mb-1 gene product, the other molecules associated with the human receptor have not been identified. In this report we characterize the phosphoproteins that are noncovalently associated with mIgM on human tonsillar B cells and human pre-B cell lines. mIgM is noncovalently associated with a disulfide-linked heterodimer composed of variably glycosylated forms of two core proteins with apparent molecular mass of 26.5 and 27 kDa. Western blotting analysis reveals that the lower m.w. component of each of the mIgM-associated heterodimers and its 27-kDa deglycosylated core protein are reactive with antibodies against the murine B29 gene product. Thus, a product of the B29 gene is a component of the AgR complex in human and murine B cells, occurring as a disulfide linked dimer with product(s) of the mb-1 gene. Interestingly, mb-1 and B29 gene products expressed on human cells are much more heterogenously N-glycosylated than their murine B cell counterparts.
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PMID:Human pre-B and B cell membrane mu-chains are noncovalently associated with a disulfide-linked complex containing a product of the B29 gene. 140 17

The effect of interferon-alpha on Daudi lymphoma cells either sensitive or resistant to the action of this cytokine has been analysed in terms of phospholipase C (PLC) and D (PLD) activities. Results have shown a combined modulation of PIP2-specific phospholipase C and phospholipase D. In particular, a decreased activity of PIP2-specific PLC has been found, concomitant to a PLD-mediated phosphatidylcholine hydrolysis, suggesting that the intracellular signalling activated by interferon in Daudi cells involves a phospholipase D/phosphohydrolase pathway.
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PMID:Interferon-mediated intracellular signalling. Modulation of different phospholipase activities in Burkitt lymphoma cells. 144 36

Phosphatidylinositol-specific phospholipase C (PI-PLC) treatment of the human natural killer (NK) target cells Molt-4, Jurkat, and U937 reduced their susceptibility to killing by human NK cells in a dose-dependent fashion. This indicates that a cell surface structure, anchored by a glycosyl-phosphatidylinositol (G-PI) moiety, is important in NK cytotoxicity. In contrast, another common NK target cell line, K562, remained susceptible to NK killing after enzyme treatment, suggesting that distinct target structures are expressed by this cell line. PI-PLC treatment of Molt-4 cells also reduced their sensitivity to human lymphokine activated killer (LAK) cells, suggesting that NK and LAK cells share common specificity in the killing of Molt-4. In contrast, PI-PLC had no effect on the killing of the LAK target cell line, Daudi, which is only weakly sensitive to unactivated NK cells. Killing of a variety of murine target cells by murine NK cells was not affected by PI-PLC treatment, but cross-species killing of Molt-4 by murine NK cells was inhibited by PI-PLC, suggesting a common mechanism in the killing of this human target cell line. The PI-PLC treatment of effector cells from either species did not reduce their NK activity. The reduction in sensitivity of the Molt-4, Jurkat, and U937 target cells probably results from a loss of a target specific G-PI linked membrane molecule, but other possible explanations for these results are also discussed.
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PMID:Decreased natural killer (NK) susceptibility of human NK target cells after phosphatidylinositol-specific phospholipase C treatment. 253 97

A monoclonal antibody MEM-43 was prepared, which recognizes an antigen expressed on all peripheral blood leucocytes, on erythrocytes and several cell lines, but is absent from U937, Nalm-6, Daudi and Raji cell lines. The antigen isolated by immunoaffinity chromatography from several cell lines is an 18,000-25,000 mol. wt glycoprotein. An apparently identical antigen isolated from erythrocytes binds to several lectins and has a 14,000 mol. wt polypeptide backbone, modified by an endoglycosidase F-sensitive carbohydrate moiety. The epitope recognized is reduction-sensitive. The sequence of N-terminal 17 amino acid residues was determined; five out of six N-terminal amino acids are identical to those found at the N-terminus of the mouse lymphocyte surface antigen Ly-6C. The antigen is completely released from the cell surface after treatment with phosphatidylinositol-specific phospholipase C.
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PMID:Characterization of a broadly expressed human leucocyte surface antigen MEM-43 anchored in membrane through phosphatidylinositol. 291 59

Haemolysis by Sendai virus, alpha-toxin, and activated complement is inhibited by high concentrations of divalent cations. In Daudi cells, sublytic amounts of these agents induce the following changes: collapse of surface membrane potential, uptake of Na+ and loss of K+ from cells, and leakage of phosphorylated metabolites from cells. The changes induced by Sendai virus and complement are sensitive to physiological concentrations of extracellular Ca2+. It is concluded that fluctuations in plasma Ca2+ concentration may affect the damaging action of certain pore-forming agents on susceptible cells.
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PMID:Common action of certain viruses, toxins, and activated complement: pore formation and its prevention by extracellular Ca2+. 609 41

Peptides which stimulate the formation of inositol phosphates (InoPs) in lymphocyte cell lines were identified by screening synthetic peptide libraries composed of random sequences of hexapeptides. The peptides containing the consensus sequence XKYX(P/V)M were found to be most active in the phospholipase C (PLC)-mediated formation of InoPs in a human B myeloma cell line, U266. The peptides also stimulated the phosphoinositide hydrolysis and the release of [Ca2+]i in HL60 and U937 cell lines. On the other hand, these peptides showed no effect in the following cell lines: NIH3T3, PC12, Daudi, Sp2, Jurkat, H9, Molt-4, SupT-1, K562, and RBL-2H3. The result suggests the possibility that the peptides may have cell type specificity. Experiments with one of the active peptides, WKYMVM-NH2 showed that its action mimics the effect of AlF4- which is a G-protein activator in the InoPs generation, and pertussis toxin partially blocked the InoPs accumulation and [Ca2+]i release induced by the peptide in the U266 cells. Binding assays with the peptide labeled with 125I showed that U266 cells have a saturable number of binding sites for the peptide. Taken together, these results suggest that the peptides could activate PLC-mediated signal transduction via a pertussis toxin-sensitive G-protein coupled receptor in certain cell types.
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PMID:Identification of the peptides that stimulate the phosphoinositide hydrolysis in lymphocyte cell lines from peptide libraries. 862 7

CD19 is a coreceptor on B cells that enhances the increase in cytoplasmic calcium and ERK2 activation when coligated with the B cell Ag receptor. Constructs containing point mutations and truncations were expressed in Daudi human B lymphoblastoid cells to systematically determine the requirement for individual CD19 cytoplasmic tyrosines in these responses. Evidence for activity was found for Y330, Y360, and Y421 as well as that previously published for Y391. Precipitates formed with phosphopeptides consisting of CD19 sequences flanking these residues were used to screen for cytoplasmic proteins that mediate signaling. Phosphopeptide Y330 precipitated Grb2 and Sos, whereas phosphopeptides Y391 and Y421 both precipitated Vav and phospholipase C-gamma2. These molecules also were found associated with native CD19. In mapping studies with altered constructs, CD19 Y330 and/or Y360 were necessary for binding Grb2 and Sos. Vav associated with CD19 constitutively in unstimulated cells by a tyrosine-independent mechanism requiring the portion of CD19 encoded by exons 9-12. After B cell Ag receptor stimulation, Vav association was tyrosine-dependent, but binding was influenced by multiple residues. However, when maximally phosphorylated by pervanadate, Y391 and, to a lesser extent, Y421 were sufficient. CD19 Y391 was also both necessary and sufficient for binding phospholipase C-gamma2. Thus, different tyrosines along the CD19 cytoplasmic domain provide scaffolding for the formation of complexes of different signaling molecules.
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PMID:Systematic analysis of the role of CD19 cytoplasmic tyrosines in enhancement of activation in Daudi human B cells: clustering of phospholipase C and Vav and of Grb2 and Sos with different CD19 tyrosines. 1070 2

Cross-linking of the B cell antigen receptor (BCR) results in the activation of several protein tyrosine kinases leading to phospholipase C-gamma2-dependent phospholipid hydrolysis and Ca2+ mobilization, followed by activation of the protein kinase C (PKC) family members. Sustained Ca2+ release in B lymphocytes is dependent on the membrane localization and activation of the protein tyrosine kinase BTK. Ca2+ release is a tightly regulated process involving BTK membrane localization through its phosphorylation by PKCbeta. A selective role of PKCbeta in B cell signaling was first revealed by the characterization of PKCbeta knockout mice, which displayed decreased B cell proliferation in response to various mitogenic stimuli. However, it is not clear whether the B cell defects displayed by the PKCbeta knockout mice are due a B cell developmental defect or the scaffolding function of PKCbeta, resulting in a defect in the recruitment or formation of signal transducing complex molecules. Thus, in this report we investigated the effects of pharmacologic inhibition of the catalytic function of PKCbeta on B cell survival and growth. Treatment of Daudi B lymphoma cell line with a selective PKCbeta inhibitor, LY333531, inhibited anti-IgM-induced phosphorylation of BTK on Ser180 in a concentration-dependent manner, which was concomitant with an increase in BTK activation, and Ca2+ mobilization. In primary splenic B cells, LY333531 inhibited BCR-induced B cell proliferation, but did not affect basal or LPS-induced proliferation. Finally, LY333531 treatment resulted in the induction of apoptosis of anti-IgM-activated B cells, which corroborated with their inability to up-regulate pro-survival factors, Bcl-X(L) and Bcl-2. These results support the important and selective role of the PKCbeta enzymatic function in controlling Ca2+ release during BCR signaling leading to B lymphocyte survival and growth.
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PMID:Selective role of PKCbeta enzymatic function in regulating cell survival mediated by B cell antigen receptor cross-linking. 1656 96