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Query: UNIPROT:P06889 (Mol)
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Mono-ADP-ribosylation appears to be a reversible modification of proteins, which occurs in many eukaryotic and prokaryotic organisms. Multiple forms of arginine-specific ADP-ribosyltransferases have been purified and characterized from avian erythrocytes, chicken polymorphonuclear leukocytes and mammalian skeletal muscle. The avian transferases have similar molecular weights of approximately 28 kDa, but differ in physical, regulatory and kinetic properties and subcellular localization. Recently, a 38-kDa rabbit skeletal muscle ADP-ribosyltransferase was purified and cloned. The deduced amino acid sequence contained hydrophobic amino and carboxy termini, consistent with known signal sequences of glycosylphosphatidylinositol (GPI)-anchored proteins. This arginine-specific transferase was present on the surface of mouse myotubes and of NMU cells transfected with the cDNA and was released with phosphatidylinositol-specific phospholipase C. Arginine-specific ADP-ribosyltransferases thus appear to exhibit considerable diversity in their structure, cellular localization, regulation and physiological role.
Mol Cell Biochem 1994 Sep
PMID:Vertebrate mono-ADP-ribosyltransferases. 789 51

ADP-ribosylation is a reversible post-translational modification of proteins involving the addition of the ADP-ribose moiety of NAD to an acceptor protein or amino acid. NAD:arginine ADP-ribosyltransferase, purified from numerous animal tissues, catalyzes the transfer of ADP-ribose to an arginine residue in proteins. The reverse reaction, catalyzed by ADP-ribosylarginine hydrolase, removes ADP-ribose, regenerating free arginine. An ADP-ribosylarginine hydrolase, purified extensively from turkey erythrocytes, was a 39-kDa monomeric protein under denaturing and non-denaturing conditions, and was activated by Mg2+ and dithiothreitol. The ADP-ribose moiety was critical for substrate recognition; the enzyme hydrolyzed ADP-ribosylarginine and (2-phospho-ADP-ribosyl)arginine but not phosphoribosylarginine or ribosylarginine. The hydrolase cDNA was cloned from rat and subsequently from mouse and human brain. The rat hydrolase gene contained a 1086-base pair open reading frame, with deduced amino acid sequences identical to those obtained by amino terminal sequencing of the protein or of HPLC-purified tryptic peptides. Deduced amino acid sequences from the mouse and human hydrolase cDNAs were 94% and 83% identical, respectively to the rat. Anti-rat brain hydrolase polyclonal antibodies reacted with turkey erythrocyte, mouse and bovine brain hydrolase. The rat hydrolase, expressed in E. coli, demonstrated enhanced activity in the presence of Mg2+ and thiol, whereas the recombinant human hydrolase was stimulated by Mg2+ but was thiol-independent. In the rat and mouse enzymes, there are five cysteines in identical positions; four of the cysteines are conserved in the human hydrolase.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Biochem 1994 Sep
PMID:ADP-ribosylarginine hydrolases. 789 53

Several cases of ADP-ribosylation of endogenous proteins in procaryotes have been discovered and investigated. The most thoroughly studied example is the reversible ADP-ribosylation of the dinitrogenase reductase from the photosynthetic bacterium Rhodospirillum rubrum and related bacteria. A dinitrogenase reductase ADP-ribosyltransferase (DRAT) and a dinitrogenase reductase ADP-ribose glycohydrolase (DRAG) from R. rubrum have been isolated and characterized. The genes for these proteins have been isolated and sequences and show little similarity to the ADP-ribosylating toxins. Other targets for endogenous ADP-ribosylation by procaryotes include glutamine synthetase in R. rubrum and Rhizobium meliloti and undefined proteins in Streptomyces griseus and Pseudomonas maltophila.
Mol Cell Biochem 1994 Sep
PMID:Reversible ADP-ribosylation as a mechanism of enzyme regulation in procaryotes. 789 54

A cellular ADP-ribosyltransferase activity has been found in a variety of animals and tissues. The enzyme transfers ADP-ribose from NAD to elongation factor 2, inactivating the factor and thus inhibiting in vitro protein synthesis. Although, the mechanism of action of the cellular enzyme appears similar to diphtheria toxin and Pseudomonas exotoxin A, it differs from the toxins in that only a fraction of the EF-2 pool is modified. The endogenously ADP-ribosylated EF-2 has been detected by a variety of methods including two-dimensional electrophoresis and immunoprecipitation with elongation factor 2 antibody. The nature of the cellular ADP-ribosyltransferase and its physiological significance are unknown.
Mol Cell Biochem 1994 Sep
PMID:Cellular ADP-ribosylation of elongation factor 2. 789 55

Nitric oxide (NO) has been suggested to act as a regulator of endogenous intracellular ADP-ribosylation, based on radiolabelling of proteins in tissue homogenates incubated with [32P]NAD and NO. After the NO-stimulated modification was replicated in a defined system containing only the purified acceptor protein, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), the hypothesis of NO-stimulation of an endogenous ADP-ribosyltransferase became moot. The NO-stimulated, NAD-dependent modification of GAPDH was recently characterized as covalent binding of the whole NAD molecule to the enzyme, not ADP-ribosylation. With this result, along with the knowledge that GAPDH is stoichiometrically S-nitrosylated, the role of NO in protein modification with NAD may be viewed as the conferring of an unexpected chemical reactivity upon GAPDH, possibly due to nitrosylation of a cysteine in the enzyme active site.
Mol Cell Biochem 1994 Sep
PMID:Nitric oxide and NAD-dependent protein modification. 789 64

Mono-ADP-ribosylation is a protein modification that occurs at a number of different amino acids, dictated by the specificity of the individual ADP-ribosyltransferases. A specific cysteine in several guanine nucleotide-binding regulatory proteins is ADP-ribosylated by the bacterial protein pertussis toxin. Recent purification of an ADP-ribosylcysteine hydrolase and NAD:cysteine ADP-ribosyltransferase, and detection of ADP-ribose-cysteine linkages in tissue samples has raised hope that an endogenous regulatory cysteine-specific ADP-ribosylation pathway exists. A current goal is the identification of such a pathway for ADP-ribosylation of cysteine within animal cells. Interpretation of the data in this field has been complicated by recent reports that revealed several unforeseen chemical reactions of NAD and its metabolites with free cysteine and cysteine in proteins. This mini-review covers the latest understanding of the ADP-ribosylation reactions associated with cysteine, and provides a set of criteria for future research to establish positively the existence of an endogenous cysteine-specific mono-ADP-ribosyltransferase.
Mol Cell Biochem 1994 Sep
PMID:Enzymatic and nonenzymatic ADP-ribosylation of cysteine. 789 67

The mechanism by which NAD stimulates cardiac adenylate cyclase was investigated. In highly purified canine cardiac sarcolemma, NAD stimulated adenylate cyclase activity in the presence of agents which activate Gs (i.e. 5 mM AlF4-, 10 microM GTP gamma S, 10 microM GppNHp or isoproterenol plus 2 nM GTP gamma S). Furthermore, the EC50 of isoproterenol to stimulate adenylate cyclase was reduced in the presence of NAD. In membranes incubated with [32P]-NAD, AlF4-, 10 microM GTP gamma S or isoproterenol plus 2 nM GTP gamma S produced a selective increase in the radiolabeling of a single 45-kDa protein which was identified as Gs alpha by immunoprecipitation. Cholera toxin catalysed radiolabeling of the same protein. Neutral hydroxylamine released [32P]-ADP-ribose from Gs alpha prelabeled in the presence of AlF4- and [32P]-NAD indicating that an arginine residue on Gs alpha was modified by an endogenous ADP-ribosyltransferase. ADP-ribosyltransferase inhibitors, novobiocin, vitamin K1 or 3-aminobenzamide, inhibited AlF4- stimulated ADP-ribosylation of Gs alpha and NAD potentiation of adenylate cyclase with similar efficacies. The activity responsible for NAD potentiation of adenylate cyclase and ADP-ribosylation of Gs alpha was not removed under hypotonic or hypertonic conditions and therefore appears to be tightly membrane bound. Collectively, these observations indicate that canine cardiac sarcolemma possess an ADP-ribosyltransferase which may constitutively catalyse transfer of an ADP-ribose to activated Gs alpha.
J Mol Cell Cardiol 1994 Feb
PMID:Modification of cardiac membrane adenylate cyclase activity and Gs alpha by NAD and endogenous ADP-ribosyltransferase. 800 86

We observed dilution/vortex-mixing-induced inactivation of arginine-specific ADP-ribosyltransferase purified from chicken peripheral polymorphonuclear granulocytes (heterophils) and re-activation of the less active form by dithiothreitol plus NaCl, under anaerobic conditions. The vortex-mixing-induced inactivation of the diluted enzyme was rapid; more than 85% of the enzyme activity was lost with 1-min vortex-mixing at room temperature. When the less-active form of the enzyme was treated with 10 mM dithiothreitol plus 0.2 M NaCl, under anaerobic conditions, more than 50% of the enzyme activity was restored. Putative mechanisms of the vortex-mixing-induced inactivation and dithiothreitol/NaCl-dependent re-activation of the arginine-specific ADP-ribosyltransferase are discussed.
Biochem Mol Biol Int 1994 Feb
PMID:Vortex-mixing-induced inactivation of arginine-specific ADP-ribosyltransferase activity and re-activation of the less-active form by dithiothreitol plus NaCl under anaerobic conditions. 801 26

Evidence is accumulating that rho p21, a ras p21-related small GTP-binding protein (G protein), regulates the actomyosin system. The actomyosin system is known to be essential for cell motility. In the present study, we examined the action of rho p21, its inhibitory GDP/GTP exchange protein (named rho GDI), its stimulatory GDP/GTP exchange protein (named smg GDS), and Clostridium botulinum ADP-ribosyltransferase C3, known to selectively ADP-ribosylate rho p21 and to impair its function, in cell motility (chemokinesis) of Swiss 3T3 cells. We quantitated the capacity of cell motility by measuring cell tracks by phagokinesis. Microinjection of the GTP gamma S-bound active form of rhoA p21 or smg GDS into Swiss 3T3 cells did not affect cell motility, but microinjection of rho GDI into the cells did inhibit cell motility. This rho GDI action was prevented by comicroinjection of rho GDI with the GTP gamma S-bound form of rhoA p21 but not with the same form of rhoA p21 lacking the C-terminal three amino acids which was not posttranslationally modified with lipids. The rho GDI action was not prevented by Ki-rasVal-12 p21 or any of the GTP gamma S-bound form of other small GTP-binding proteins including rac1 p21, G25K, and smg p21B. Among these small G proteins, rhoA p21, rac1 p21, and G25K are known to be substrates for rho GDI. The rho GDI action was not prevented by comicroinjection of rho GDI with smg GDS. Microinjection of C3 into Swiss 3T3 cells also inhibited cell motility. These results indicate that the rho GDI-rho p21 system regulates cell motility, presumably through the actomyosin system.
Mol Cell Biol 1993 Jan
PMID:Involvement of rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI) in cell motility. 841 62

ADP-ribosylation factors (ARFs) are approximately 20-kDa guanine nucleotide-binding proteins that are allosteric activators of the NAD:arginine ADP-ribosyltransferase activity of cholera toxin and appear to play a role in intracellular vesicular trafficking. Although the physiological roles of these proteins have not been defined, it has been presumed that each has a specific intracellular function. To obtain genetic evidence that each ARF is under evolutionary pressure to maintain its structure, and presumably function, rat ARF cDNA clones were isolated and their nucleotide and deduced amino acid sequences were compared to those of other mammalian ARFs. Deduced amino acid sequences for rat ARFs 1, 2, 3, 5 and 6 were identical to those of the known cognate human and bovine ARFs; rat ARF4 was 96% identical to human ARF4. Nucleotide sequences of both the untranslated as well as the coding regions were highly conserved. These results indicate that the ARF proteins are, as a family, extraordinarily well conserved across mammalian species. The unusually high degree of conservation of the untranslated regions is consistent with these regions having important regulatory roles and that individual ARFs contain structurally unique elements required for specific functions.
Mol Cell Biochem 1996 Jun 07
PMID:Interspecies relationships among ADP-ribosylation factors (ARFs): evidence of evolutionary pressure to maintain individual identities. 881 5


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