ADP-ribosylation factor GTPases in signal transduction and membrane traffic: independent functions?

1999 ◽  
Vol 27 (4) ◽  
pp. 642-647 ◽  
Author(s):  
D. Jones ◽  
B. Bax ◽  
S. Cockcroft
Keyword(s):  
Signal Transduction ◽  
Membrane Traffic ◽  
Adp Ribosylation ◽  
Independent Functions ◽  
Adp Ribosylation Factor

scholarly journals Resolution of two ADP-ribosylation factor 1 GTPase-activating proteins from rat liver

1997 ◽  
Vol 324 (2) ◽  
pp. 413-419 ◽  
Author(s):  
Paul A. RANDAZZO
Keyword(s):  
Dissociation Constant ◽  
Rat Liver ◽  
Potential Role ◽  
Membrane Traffic ◽  
Adp Ribosylation ◽  
Substrate Preferences ◽  
Gtpase Activating Proteins ◽  
Gtp Binding ◽  
Adp Ribosylation Factor

ADP-ribosylation factor 1 (ARF1) is a 21 kDa GTP-binding protein that regulates multiple steps in membrane traffic. Here, two ARF1 GTPase-activating proteins (GAPs) from rat liver were resolved. The GAPs were antigenically distinct. One reacted with a polyclonal antibody raised against the GAP catalytic peptide previously purified by Makler et al. [Makler, Cukierman, Rotman, Admon and Cassel (1995) J. Biol. Chem. 270, 5232–5237], and here is referred to as GAP1. The other GAP (GAP2) did not react with the antibody. These GAPs differed in phospholipid dependencies. GAP1 was activated 3–7-fold by the acid phospholipids phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidic acid (PA) and phosphatidylserine (PS). In contrast, GAP2 was stimulated 20–40-fold by PIP2. PA and PS had no effect by themselves but PA increased GAP2 activity in the presence of PIP2. The GAPs were otherwise similar in activity. In the presence of phosphoinositides, the Km of GAP1 for ARF1–GTP was estimated to be 8.1±1.6 μM and the dissociation constant for ARF1–guanosine 5′,3-O-(thio)triphosphate (GTP[S]) was 7.4±2.2 μM. GAP2 was similar with a Km for ARF1–GTP of 5.4±1.2 μM and a dissociation constant for ARF1–GTP[S] of 4.8±0.3 μM. Similarly, no differences were found in substrate preferences. Both GAP1 and GAP2 used ARF1 and ARF5 as substrates but not ARF6 or ARF-like protein-2. The potential role of multiple ARF GAPs in the independent regulation of ARF at specific steps in membrane traffic is discussed.

Arf family GTPases: roles in membrane traffic and microtubule dynamics

2005 ◽  
Vol 33 (6) ◽  
pp. 1269-1272 ◽  
Author(s):  
R.A. Kahn ◽  
L. Volpicelli-Daley ◽  
B. Bowzard ◽  
P. Shrivastava-Ranjan ◽  
Y. Li ◽  
...  
Keyword(s):  
Phylogenetic Analysis ◽  
Family Members ◽  
Membrane Traffic ◽  
Microtubule Dynamics ◽  
Database Mining ◽  
Vesicle Traffic ◽  
Adp Ribosylation ◽  
Adp Ribosylation Factor ◽  
In Cells

Database mining and phylogenetic analysis of the Arf (ADP-ribosylation factor) superfamily revealed the presence in mammals of at least 22 members, including the six Arfs, two Sars and 14 Arl (Arf-like) proteins. At least six Arf family members were found in very early eukaryotes, including orthologues of Arf, Sar, Arl2, Arl3, Arl6 and Arl8. While roles for Arfs in membrane traffic are well known, those for most of the Arls remain unknown. Depletion in cells of the most closely related human Arf proteins, Arf1–Arf5, reveals specificities among their cellular roles and suggests that they may function in pairs at different steps in endocytic and secretory membrane traffic. In addition, recent results from a number of laboratories suggest that several of the Arl proteins may be involved in different aspects of microtubule-dependent functions. Thus, a second major role for Arf family GTPases, that of regulating microtubules, is emerging. Because membrane traffic is often dependent upon movement of vesicles along microtubules this raises the possibility that these two fundamental functions of Arf family members, regulation of vesicle traffic and microtubule dynamics, diverged from one function of Arfs in the earliest cells that has continued to branch and allow additional levels of regulation.

scholarly journals ADP ribosylation factor 1 mutants identify a phospholipase D effector region and reveal that phospholipase D participates in lysosomal secretion but is not sufficient for recruitment of coatomer I

1999 ◽  
Vol 341 (1) ◽  
pp. 185-192 ◽  
Author(s):  
David H. JONES ◽  
Ben BAX ◽  
Amanda FENSOME ◽  
Shamshad COCKCROFT
Keyword(s):  
Signal Transduction ◽  
Phospholipase D ◽  
Signal Transduction Pathway ◽  
High Molecular Mass ◽  
Deletion Mutants ◽  
Amino Acid Residues ◽  
Transduction Pathway ◽  
Wild Type ◽  
Adp Ribosylation ◽  
Adp Ribosylation Factor

The small GTP-binding protein, ADP-ribosylation factor 1 (ARF1) is essential for the formation of coatomer-coated vesicles from the Golgi and is also an activator of phospholipase D (PLD). Moreover, ARF1-regulated PLD is part of the signal-transduction pathway that can lead to secretion. In this study, substitution and deletion mutants of ARF1 were tested for their ability to activate PLD. These map the PLD effector region of ARF1 to the α2 helix, part of the β2-strand and the N-terminal helix and its ensuing loop. ARF mutants with an increased or decreased ability to activate PLD showed similar characteristics when tested for their ability to stimulate secretion from HL60 cells. ARF1, deleted of the N-terminal 17 amino acid residues (Ndel17), did not support PLD activity or secretion, and neither did it inhibit the activity of wild-type myristoylated ARF1 (myrARF1). In contrast, Ndel17 effectively competed with wild-type myrARF1 to prevent coatomer binding to membranes. This appears to define a structural role for Ndel17, as it can bind a high-molecular mass complex in cytosol. In addition, ethanol has no effect on recruitment of coatomer to membrane. We conclude that the function of ARF-regulated PLD is in the signal-transduction pathway leading to secretion of lysosomal granules, and not as an essential component of ARF1-mediated coatomer binding.

ADP-ribosylation factor-like 8b is required for the development of mouse models of systemic lupus erythematosus

2019 ◽  
Vol 31 (4) ◽  
pp. 225-237
Author(s):  
Shin-Ichiroh Saitoh ◽  
Yoshiko Mori Saitoh ◽  
Kenji Kontani ◽  
Katsuaki Sato ◽  
Kensuke Miyake
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Mouse Models ◽  
Lupus Erythematosus ◽  
Systemic Lupus ◽  
Adp Ribosylation ◽  
Adp Ribosylation Factor
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