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)

RT6 proteins are glycosylphosphatidylinositol (GPI)-linked alloantigens that are localized to cytotoxic T lymphocytes and that have nicotinamide adenine dinucleotide glycohydrolase and adenosine diphosphate (ADP)-ribosyltransferase activities. In view of the importance of GPI-linked surface proteins in mediating interactions of cells with their milieu, and the varied functions of airway cells in inflammation, we undertook the present study to determine whether human homologues of the RT6 superfamily of ADP-ribosyltransferases (ART) are expressed in pulmonary epithelial cells. We hypothesized that these surface proteins or related family members may be present in cells that interact with inflammatory cells, and that they may thereby be involved in intercellular signaling. Using in situ analysis and Northern blot analysis, we identified ART1 messenger RNA (mRNA) in airway epithelial cells. As expected for GPI-anchored proteins, the localization of ART1 at the apical surface of ciliated epithelial cells was demonstrated by staining with polyclonal anti-ART1 antibody, and was confirmed by loss of this immunoreactivity after treatment with phosphatidylinositol-specific phospholipase C (PI-PLC), which selectively cleaves GPI anchors and releases proteins from the plasma membrane. Using in situ hybridization with specific ART3 and ART4 oligonucleotides, we also identified two additional members of the RT6 superfamily in epithelial cells. In accord with these findings, we identified ART3 and ART4 mRNAs through reverse transcription- polymerase chain reaction of polyadenine-positive RNA from human trachea. Interestingly, these proteins appeared to be preferentially localized to the airway epithelium. The localized expression of these members of the RT6 superfamily in human pulmonary epithelial cells may reflect a role for them in cell-cell signaling during immune responses within the airway.
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PMID:Selective expression of RT6 superfamily in human bronchial epithelial cells. 1046 Jul 51

Mono-ADP-ribosyltransferase (ART) 4 belongs to a family of ectoenzymes that catalyze the transfer of ADP-ribose from NAD+ to a target protein. ART4 could be detected on HEL cells and erythrocytes by FACS analysis while it was absent from activated monocytes, despite the presence of ART4 mRNA in these cells. The predicted glycosylphosphatidylinositol (GPI) linkage of ART4 could be verified by showing that treatment of erythrocytes, HEL cells and ART4-transfected HEK-293-T cells with phosphatidylinositol-specific phospholipase C results in a decrease in ART4 expression. Furthermore, an ART4 construct carrying an Ala285Val mutation that is critical for the formation of a GPI anchor failed to be expressed in transfected C-33A cells. Analysis of the gene structure revealed that the first of the three exons was at least 236 bp longer than previously published and that splicing occurred in the coding region of the mRNA from HEL cells and monocytes. When carrying out 5' inverse RACE-PCR we confirmed the existence of 5 ATGs in the 5' untranslated region (5'UTR). By deletion and site-directed mutagenesis of the ATGs, we showed that the first two ATGs impair translation and that both the 3rd and 5th ATG can be used for translation initiation after expression in C-33A cells. On analysis of the 3'UTR, which contains 2 adenylate/uridylate-rich elements (AREs), we detected one variant in monocytes that would be devoid of a GPI-anchor signal and thus could represent a secreted form of ART4. Thus, alternative splicing and the use of regulatory elements in the 5'UTR and 3'UTR represent means to control ART4 expression.
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PMID:Analysis of mono-ADP-ribosyltransferase 4 gene expression in human monocytes: splicing pattern and potential regulatory elements. 1614 Apr 4

Epithelial cells lining human airways and cells recruited to airways participate in the innate immune response in part by releasing human neutrophil peptides (HNP). Arginine-specific ADP-ribosyltransferases (ART) on the surface of these cells can catalyze the transfer of ADP-ribose from NAD to proteins. We reported that ART1, a mammalian ADP-ribosyltransferase, present in epithelial cells lining the human airway, modified HNP-1, altering its function. ADP-ribosylated HNP-1 was identified in bronchoalveolar lavage fluid (BALF) from patients with asthma, idiopathic pulmonary fibrosis, or a history of smoking (and having two common polymorphic forms of ART1 that differ in activity), but not in normal volunteers or patients with lymphangioleiomyomatosis. Modified HNP-1 was not found in the sputum of cystic fibrosis patients or in leukocyte granules of normal volunteers. The finding of ADP-ribosyl-HNP-1 in BALF but not in leukocyte granules suggests that the modification occurred in the airway. Most of the HNP-1 in the BALF from individuals with a history of smoking was, in fact, mono- or di-ADP-ribosylated. ART1 synthesized in Escherichia coli, glycosylphosphatidylinositol-anchored ART1 released with phosphatidylinositol-specific phospholipase C from transfected NMU cells, or ART1 expressed endogenously on C2C12 myotubes modified arginine 14 on HNP-1 with a secondary site on arginine 24. ADP-ribosylation of HNP-1 by ART1 was substantially greater than that by ART3, ART4, ART5, Pseudomonas aeruginosa exoenzyme S, or cholera toxin A subunit. Mouse ART2, which is an NAD:arginine ADP-ribosyltransferase, was able to modify HNP-1, but to a lesser extent than ART1. Although HNP-1 was not modified to a significant degree by ART5, it inhibited ART5 as well as ART1 activities. Human beta-defensin-1 (HBD1) was a poor transferase substrate. Reduction of the cysteine-rich defensins enhanced their ability to serve as ADP-ribose acceptors. We conclude that ADP-ribosylation of HNP-1 appears to be primarily an activity of ART1 and occurs in inflammatory conditions and disease.
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PMID:ADP-ribosyltransferase-specific modification of human neutrophil peptide-1. 1662 71