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)

ADP-ribosylation of protein in heart membrane preparations has been shown to be present in adult tissue but absent from early neonate tissue [Piron and McMahon (1990) Biochem. J. 270, 591-597]. To further this observation, the cardiac membrane-bound form of arginine-specific mono-ADP-ribosyltransferase (EC 2.4.2.31) has been characterized. Apparent Km values of 330 and 470 microM were found in heart membrane preparations from rat and quail respectively. The Vmax. value depended greatly on the species of animal studied, and was 1.1 and 48 nmol/min per mg in rat and quail preparations respectively. The specific activity of the enzyme was lowest in pig, intermediate in rat, dog and rabbit, and highest in mouse and quail cardiac membranes. In the rat, the ADP-ribosylation of protein and enzyme activity were very low in heart preparations from 1-15-day-old animals. Thereafter the ADP-ribosylation and enzyme activity increased gradually to adulthood. Bacillus cereus phosphatidylinositol-specific phospholipase C, known to hydrolyse glycosylphosphatidylinositol anchors of proteins, released the mono-ADP-ribosyltransferase from membrane preparations of both rat and quail in a dose-dependent, Zn(2+)-inhibited manner. Thus it appears that a membrane-bound form of arginine-specific mono-ADP-ribosyltransferase is present in heart membranes from a variety of species and is not species-specific. The activity of this ADP-ribosyltransferase appears to be developmentally regulated and to be bound to the cardiac membranes by a glycosylphosphatidylinositol anchor.
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PMID:Developmental and biochemical characteristics of the cardiac membrane-bound arginine-specific mono-ADP-ribosyltransferase. 839 92

Many cell surface proteins are anchored into the cell membrane by glycosylphosphatidylinositol (GPI), among those a recently discovered arginine-specific mono-ADP-ribosyltransferase on cytotoxic T cells (CTL). This enzyme transfers ADP-ribose to cell surface proteins resulting in inhibition of cytotoxic and proliferative activity. Here we report that ADP-ribosyltransferase is released in active forms by crosslinking CD3, exposure to Il-2 or PMA stimulation. Release of transferase is specific, as another GPI-anchored protein, Thy-1 is not released. Transferase molecules released by cell activation are indistinguishable in size from molecules released by phospholipase C, suggesting that the release mechanism acts close to or within the GPI anchor. Protease inhibitors fail to inhibit transferase release with exception of 1,10-phenanthroline and its 4,7-diphenyl derivative. This suggests that the release mechanism acts on the cell surface but does not discriminate between action of a metalloprotease or phospholipase D. Release of transferase is shown to be rapid, it is not suppressed by monensin or brefeldin A and independent of serum phospholipase D, consistent with a mechanism acting on the cell surface. Transferase expression is shown to be dependent on the cell activation stage. In CTL clones, the transferase is demonstrable as a phospholipase C releasable molecule at early but not later stages of Ag specific activation.
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PMID:Release of a glycosylphosphatidylinositol-anchored ADP-ribosyltransferase from cytotoxic T cells upon activation. 859 99

Receptor-mediated activation of T lymphocytes involves protein phosphorylation by several protein tyrosine kinases, among those the src-related enzymes p56lck and p59fyn. Accumulating evidence supports the notion that these enzymes are regulated by tyrosine phosphorylation and dephosphorylation, but much is yet to be learned about regulation of their activity. Here we demonstrate that p56lck but not p59fyn exists as a complex with a 40-kDa protein, which in its ADP-ribosylated form inhibits p56lck kinase activity. ADP-ribosylation of this protein is mediated by an arginine-specific mono-ADP-ribosyltransferase, which makes use of extracellular nicotinamide adenine dinucleotide (NAD). This enzyme is a glycosyl-phosphatidylinositol-anchored protein releasable from the surface of cytotoxic T cells by glycosyl-phosphatidylinositol-specific phospholipase C. Release of arginine-specific mono-ADP-ribosyltransferase results in failure of extracellular NAD to downmodulate p56lck kinase activity. Concomitant to suppression of the kinase by NAD, CD8 mediated transmembrane signaling and p56lck kinase activation are inhibited.
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PMID:Regulation of CTL by ecto-nictinamide adenine dinucleotide (NAD) involves ADP-ribosylation of a p56lck-associated protein. 860 1

Post-translational modifications are important in regulating the functions of signal proteins. This is well established for intracellular proteins, but little is known in the case of extracellular domains of cell surface molecules. We recently described a cell surface protein, mono-ADP-ribosyltransferase (ADPRT), on cytotoxic T cells and showed that it mediates attachment of ADP-ribose to cell surface proteins. Concomitantly, cytolytic activity and cell proliferation are inhibited. Here we report that one of the principal proteins modified by this enzyme is lymphocyte function-associated molecule-1 (LFA-1). While both chains are ADP-ribosylated on the extracellular domain of the molecule, persistence of the modification differs between the chains. Label is released from the beta-chain by 1 h, yet remains for at least 6 h on the alpha-chain. Loss of label is suppressed by phosphodiesterase inhibitors such as ADP-ribose and p-nitrophenylthymidine 5'-monophosphate, pointing to the involvement of this class of enzyme. Modification of LFA-1 requires expression of the cell surface ADPRT and causes the loss of epitopes recognized by alpha- and beta-chain-specific Abs. Concomitantly, the generation of inositol phosphates induced by Ab cross-linking of LFA-1 is significantly inhibited. Consistent with this effect, anti-LFA-1-induced homotypic cell adhesion is also inhibited. These effects are not seen in cells from which the ADPRT was removed by phospholipase C. Moreover, cells lacking the cell surface ADPRT are not inhibited by NAD in the cell adhesion assay, but gain this property upon transfection with the ADPRT gene. It is concluded that the cell surface protein mono-ADPRT regulates LFA-1 functions.
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PMID:Cell surface ADP-ribosyltransferase regulates lymphocyte function-associated molecule-1 (LFA-1) function in T cells. 887 30