Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Cyclic ADP-Ribose”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

867 records · Page 49Linked to original sources
PubMed1984

Characterization of transducin from bovine retinal rod outer segments. Mechanism and effects of cholera toxin-catalyzed ADP-ribosylation.

Transducin, a guanine nucleotide-binding protein consisting of two subunits (T alpha and T beta gamma), mediates the signal coupling between rhodopsin and a membrane-bound cyclic GMP phosphodiesterase in retinal rod outer segments. The T alpha subunit is an activator of the phosphodiesterase, and the function of the T beta gamma subunit is to physically link T alpha with photolyzed rhodopsin. In this study, the mechanism of cholera toxin-catalyzed ADP-ribosylation of T alpha has been examined in a reconstituted system consisting of purified transducin and stripped rod outer segment membranes. Limited proteolysis of the labeled T alpha with trypsin indicated that the inserted ADP-ribose is located exclusively on a single proteolytic fragment with an apparent molecular weight of 23,000. Maximal incorporation of ADP-ribose was achieved when guanosine 5'-(beta, gamma-imido)triphosphate (Gpp(NH)p) and T beta gamma were present at concentrations equal to that of T alpha and when rhodopsin was continuously irradiated with visible light in the 400-500 nm region. The stimulating effect of illumination was related to the direct interaction of the retinal chromophore with opsin. These findings strongly suggest that a transient protein complex consisting of T alpha X Gpp(NH)p, T beta gamma, and a photointermediate of rhodopsin is the required substrate for cholera toxin. Single turnover kinetic measurements demonstrated that the ADP-ribosylation of T alpha coincided with the appearance of a population of transducin molecules having a very slow rate of GTP hydrolysis. The hydrolysis rate of the bound GTP for this population was 1.1 X 10(-3)/s, which was 22-fold slower than the rate for the unmodified transducin.

Adenosine Diphosphate Ribose↗
PubMed1994

Stimulatory guanine nucleotide binding protein in pig epidermis: transient increase of the 45KDA cholera toxin substrate (Gs alpha) in the tape stripping-induced hyperproliferative state.

Cholera toxin catalyzed the transfer of ADP-ribose from [alpha-32P] NAD to 45kDa protein in pig epidermis. Western blot analysis using anti-Gs alpha antibody identified the 45kDa protein to be Gs alpha. In contrast to pertussis toxin-catalyzed ADP-ribosylation of Gi alpha, the cholera toxin-catalyzed ADP-ribosylation was enhanced by the presence of Mg2+ in the reaction mixture. The cholera toxin-catalyzed ADP-ribosylation of the epidermal 45kDa membrane protein was significantly decreased, when samples were prepared from the cholera toxin-pretreated epidermis. The results, coupled with our previous report (Tsutsui and Iizuka 1990), indicate that pig epidermis contains functional G proteins (Gs and Gi), that affect the epidermal adenylate cyclase activity. Tape stripping-induced hyperproliferative epidermis showed an increased cholera toxin-catalyzed ADP-ribosylation of the 45kDa protein (Gs alpha) at 12-24 h following the tape stripping. Immunoblot analysis, however, showed no remarkable change in the level of Gs alpha compared with non-stripping controls. There was no significant difference in the level of the pertussis toxin-induced ADP-ribosylation of 40kDa protein (Gi alpha) in the tape-stripped epidermis. Immunoblot analysis showed no change in Gi content, either. Forskolin-induced cyclic AMP accumulation was markedly increased in the tape stripping-induced hyperproliferative epidermis. Cholera toxin-induced cyclic AMP accumulation was slightly increased, but this was not statistically significant. These results indicate that the alteration of Gs that is documented by cholera toxin-catalyzed ADP-ribosylation, is among the functional derangements of adenylate cyclase of tape stripping-induced hyperproliferative epidermis.

Adenosine Diphosphate Ribose↗
PubMed1995

CD38-mediated ribosylation of proteins.

The lymphocyte cell-surface Ag CD38 catabolizes NAD to adenosine 5' diphosphoribose (ADPR) and cyclic ADPR (cADPR). We show here that the soluble extracellular domain of CD38 (sCD38) mediates ADP ribosylation of several proteins. This was demonstrated by mass spectrometric analyses which revealed the addition of mass in units of 541.1 Da to these proteins, presumably corresponding to the covalent attachment of one or more ADPR moieties. Separate experiments showed that the same proteins became specifically radiolabeled following incubation with [32P]NAD plus sCD38. Additionally, it is shown that sCD38 can autoribosylate. Moreover, sCD38-mediated protein ribosylation was found to occur specifically at cysteine residues, since it was effectively blocked by addition of L-cysteine but not by other amino acids, and CD38-mediated protein ribosylation could be reversed by the addition of HgCl2, which specifically cleaves thiol-glycosidic bonds. ADPR purified from the reaction of sCD38 with NAD could itself be covalently transferred to target proteins at rates similar to the sCD38-mediated reaction, indicating that the ribosylation proceeds via the generation of this reactive intermediate. In vitro mutagenesis of a catalytic Glu residue that is conserved in numerous ADP-ribosyl transferases revealed that this amino acid is also important for catalysis in CD38. These data suggest that CD38 has the potential to cause ribosylation of experimental proteins, and raises the possibility that its specific ribosylation of a currently unidentified lymphocyte protein may contribute to its array of immunoregulatory activities.

ADP-ribosyl Cyclase↗