The Biology of ADP-Ribosylation Factors
Adenosine diphosphate (ADP) ribosylation factor (ARF) was originally defined as an activity required for the efficient activation of the purified, stimulatory, regulatory component of adenylyl cyclase, Gs, by cholera toxin (Schleifer et al. 1982; Kahn 1989, 1991). The toxin catalyzes the covalent addition of the ADP-ribose moiety of nicotinamide adenine dinucleotide (NAD) onto the α subunit of Gs. The consequences of this modification include decreased intrinsic GTP hydrolysis by the Gs protein (Cassel and Selinger 1979) and its consequent activation and subunit dissociation (Kahn and Gilman 1984a). Thus, while GTP alone is normally a very weak stimulator of membrane cyclase, after ADP-ribosylation GTP is nearly as potent as the slowly hydrolyzable analogs of GTP, e. g., GTPγS or Gpp(NH)p.
KeywordsHydrolysis Magnesium Fluoride Glycine Cysteine
Unable to display preview. Download preview PDF.
- Cavenagh MM, Kahn RA (1993) Requirement for ARF in the sporulation process of S. cerevisiae (in preparation)Google Scholar
- Kahn RA (1989) The ADP-ribosylation factor of adenylate cyclase: a 21kDa GTP-binding protein. In: Birnbaumer L, Iyengar R (eds) G-Proteins. Academic, OrlandoGoogle Scholar
- Kahn RA (1991) Quantitation and purification of ADP-ribosylation factor. In: Johnson RA, Corbin JD (eds) Methods in enzymology, vol 195. Academic, OrlandoGoogle Scholar
- Kahn RA, Rulka C (1992) Association of a GTP-binding protein (ARF) with phospholipid vesicles is controlled by guanine nucleotide binding. J Biol Chem (submitted)Google Scholar
- Kahn RA, Randazzo PA, Serafini T, Weiss O, Rulka C, Clark J, Amherdt M, Roller PP, Orci L, Rothman JE (1992b) The amino terminus of ADP ribosylation factor (ARF) is a critical determinant of ARF activities and is a potent and specific inhibitor of protein transport. J Biol Chem 267:13039–13046PubMedGoogle Scholar
- Price SR, Nightingale M, Tsai S, Williamson KC, Adamik R, Chen H, Moss J, Vaughan M (1988) Guanine nucleotide-binding proteins that enhance choleragen ADP-ribosyltransferase activity: nucleotide and deduced amino acid sequence of an ADP-ribosylation factor cDNA. Proc Natl Acad Sci USA 85:5488–5491PubMedCrossRefGoogle Scholar
- Zhang C-J, Clark J, Rulka C, Kahn RA (1993) Mutational analysis of yeast ARF1 (in preparation)Google Scholar