ADP-ribosylation factors ARFs

Cholera toxin catalyzes the ADP-ribosylation of a specific arginine residue in G and Gat. This covalent modification inhibits the intrinsic GTPase activity of these a subunits and thereby freezes them in their activated, or free, state (Fig. 19-1C). By this mechanism, cholera toxin stimulates adenylyl cyclase activity and photoreceptor transduction mechanisms. The ability of cholera toxin to ADP-ribosylate G may require the presence of a distinct protein, ADP-ribosylation factor (ARF). ARF, which is itself a small G protein (Table 19-2), also is ADP-ribosylated by cholera toxin. ARF is implicated in controlling membrane vesicle trafficking (see Ch. 9). 

ADP (Adenosine diphosphate) 536 in adenylate system 302 - 304 complexes with metal ions 296 dissociation as acid 288 intracellular concentration 304 P-31 NMR spectrum 642 pka value of 293 in regulation 535 ADP-ribose (ADPR) 315, 778, 780 ADP-ribosylation 545, 778 ADP-ribosylation factors (ARFs) 559 Adrenaline (epinephrine) 534, 542, 553, 553s in adrenergic receptor 535 a-Adrenergic receptors 553, 558, 563 p-Adrenergic receptors 553, 554 in asthma 553 in heart failure 553 receptor kinase 553 structure (proposed) 534, 555 topology 555... 

A somewhat similar zinc site is seen in one of the ADP ribosylation factors (ARFs), which are members of the Ras superfamily of GTP-binding proteins. Sequences of ARF-GAP domains show no recognizable similarity to those of... 

Cholera toxin and the very similar (in structure and mechanism of action) heat-labile enterotoxin from E. coli (LT-1 or LT, which is responsible for the syndrome of traveler s diarrhea) have been widely applied as molecular tools to facilitate understanding of signalling systems. Examples of molecules besides Gs that were identified because of work on CT are the ADP-ribosylation factors (ARFs), now known to play a critical role in intracellular vesicular transport (Moss and Vaughan, 1995), and the mammalian ADP-ribosyltransferases (Zolkiewska et al., 1994). As more is learned about CT structure and biochemistry, modified or mutant CT and LT molecules are being gen-... 

Bobak DA, Bliziotes MM, Noda M, et of. (1990) Mechanism of activation of cholera toxin by ADP-ribosylation factor (ARF) Both low- and high-affinity interactions of ARF with guanine nucleotides promote toxin activation. In Biochemistry 29 855-861. 

Price SR, Welsh CF, Haun RS, et al. (1992) Effects of phospholipid and GTP on recombinant ADP-ribosylation factors (ARFs) Molecular basis for differences in requirements for activity of mammalian ARFs. In J. Biol. Chem. 267 17766-17772. 

Randazzo PA, Terui T, Sturch S, et al. (1994) The amino terminus of ADP-ribosylation factor (ARF) 1 is essential for the interaction of Gs and ARF GTPase-activating protein. In J. Biol. Chem. 269 29490-29494. 

Engel T, Lueken A, Bode G, et al. (2004) ADP-ribosylation factor (ARF)-like 7 (ARL7) is induced by cholesterol loading and participates in apolipoprotein Al-dependent cholesterol export. FEBS Lett 566 241-246... 

The ADP-ribosylation reaction is stimulated by GTP, phospholipids, and various cellular factors, both membrane and soluble (2-9). Kahn and Gilman (7, 9) isolated a membrane protein termed ADP-ribosylation factor (ARF) that promoted the toxin-catalyzed ADP-ribosylation of Gso. The protein bound GTP in a reaction which was enhanced by NaCl and dimyristoyl phosphatidylcholine (9). It was proposed that ARF boimd directly to Gso (7) and Aat the ARF Gso complex served as the actual substrate in the toxin-catalyzed reaction (7). Tsai et cd. (10) demonstrated that ARF from bovine brain membranes activated the toxin directly rather than interacting with the substrate Gso. Other factors that enhanced the ability of choleragen to ADP-ribosylate Gso were identified in a soluble fraction from bovine brain. Two proteins that accoimted for most of the choleragen activation by the soluble fraction were resolved by ion exchange chromatography and separately purified. Each exhibited one major band by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. 

Randazzo, P. A., Miura, K., and Jackson, T. R. (2001). Assay and purification of phosphoinositide-dependent ADP-ribosylation factor (ARF) GTPase activating proteins. Regulators and effectors of small GTPases. Meth. Enzymol. 329, 343-354. 

Boehm, M., Aguilar, R. C, and Bonifacino, J. S. (2001). Functional and physical interactions of the adaptor protein complex AP-4 with ADP-ribosylation factors (ARFs). EMBO J. 20, 6265-6276. 

Morinaga, N., Tsai, S., Moss, J., and Vaughan, M. (1996). Isolation of a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP ribosylation factor (ARF) 1 and ARF3 that contains a Sec7-like domain. Proc. NatL Acad. Sci USA 93,... 

ADP-ribosylation factor domain protein 1 (ARDl) is a multifunctional protein that belongs to the family of 20-kDa ARF proteins. The ARDl gene encodes a 64-kDa protein with a structure comprising an 18-kDa ADP-ribosylation factor (ARF) domain at the C-terminus (amino acids 403-574), and a 46-kDa N-terminal domain (amino acids 1 02) that... 

Vitale, N., Chasserot-Golaz, S., Bailly, Y., Morinaga, N., Frohman, M. A., and Bader, M. F. (2002). Calcium-regulated exocytosis of dense-core vesicles requires the activation of ADP-ribosylation factor (ARF) 6 by ARF nucleotide binding site opener at the plasma membrane. J. Cell Biol. 159, 79-89. 

The ADP-ribosylation factors (ARFs) family of small GTPases regulate intracellular membrane trafficking by cycling between an inactive GDP- and an active GTP-bound form (Moss and Vaughan, 1998). In mammalian cells, the ARF family consists of six ARF isoforms (ARF 1-6). 

ARFAPTIN 2 BINDING TO RacI AND ADP-RIBOSYLATION FACTORS (ArFS) 359... 

Assays and Properties of Arfaptln 2 Binding to Racl and ADP-Ribosylation Factors (Arfs)... 

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