Structure and Function of ARF Proteins: Activators of Cholera Toxin and Critical Components of Intracellular Vesicular Transport Processes

Moss, Joel; Vaughan, Martha

doi:10.1074/jbc.270.21.12327

Cited by 300 publications

(220 citation statements)

References 52 publications

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“…3). Therefore, involvement of the amino-terminal ␣-helix of ARF1 in membrane affinity, nucleotide-induced conformational change, and effector interaction has been suggested (33, 34).…”

Section: Table Imentioning

confidence: 99%

“…ARF proteins have been implicated in vesicular membrane trafficking in several intracellular compartments, including endoplasmic reticulum, Golgi, endosomes, and nuclear envelope (reviewed in Ref. 3). ARFs are ϳ20-kDa proteins that exhibit no detectable GTPase activity (4); the ratio of GTP/GDP bound appears to be governed by guanine nucleotide-exchange proteins (GEPs) and GTPase-activating proteins (GAPs) (3).…”

mentioning

confidence: 99%

“…3). ARFs are ϳ20-kDa proteins that exhibit no detectable GTPase activity (4); the ratio of GTP/GDP bound appears to be governed by guanine nucleotide-exchange proteins (GEPs) and GTPase-activating proteins (GAPs) (3). ARF GEPs (5)(6)(7)(8)(9)(10)(11)(12) and GAPs (13)(14)(15)(16) have been both purified and cloned.…”

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confidence: 99%

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Characterization of a GDP Dissociation Inhibitory Region of ADP-ribosylation Factor Domain Protein ARD1

Vitale

Moss

Vaughan

1997

Journal of Biological Chemistry

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Although roles of G proteins 1 are enormously diverse, these GTPases all operate by a fundamentally similar mechanism (1). When GTP occupies its guanine nucleotide-binding site, the G protein can interact with and modify the activity of a downstream target protein. Hydrolysis of GTP causes the dissociation of the G protein-target complex and thus terminates the "active state" of the G protein. Cells regulate the ratio of active and inactive G proteins by modulating the rates of GDP release and GTP hydrolysis (GTPase activity).ARD1 is a 64-kDa protein that contains a 18-kDa carboxylterminal ADP-ribosylation factor (ARF) domain (p3) and a 46-kDa amino-terminal domain (p5) (2). ARF proteins have been implicated in vesicular membrane trafficking in several intracellular compartments, including endoplasmic reticulum, Golgi, endosomes, and nuclear envelope (reviewed in Ref. 3). ARFs are ϳ20-kDa proteins that exhibit no detectable GTPase activity (4); the ratio of GTP/GDP bound appears to be governed by guanine nucleotide-exchange proteins (GEPs) and GTPase-activating proteins (GAPs) (3). ARF GEPs (5-12) and GAPs (13-16) have been both purified and cloned. Inhibition of cytosolic and Golgi-associated GEPs by the fungal fatty acid metabolite brefeldin A (BFA) has been reported (5-7, 9); both BFA-insensitive and BFA-sensitive cytosolic GEPs have been isolated (8, 9). There is genetic as well as biochemical evidence that both BFA-sensitive and BFA-insensitive ARF GEPs contain a domain similar to a part of Sec7 (9 -12), a protein necessary for intra-Golgi transport.It was recently reported that the ARF domain of ARD1 binds specifically GDP and GTP, whereas the amino-terminal domain does not (17). Using recombinant proteins, it was shown that the amino-terminal p5 domain of ARD1 stimulates hydrolysis of GTP bound to the ARF domain p3 and consequently appears to be the GAP component of this bifunctional protein (18). The stimulatory effect of the p5 domain on the GTPase activity of p3 was specific, because GTP hydrolysis by other members of the ARF family was not increased (16). The presence of an intrinsic GAP domain is an apparently unique phenomenon for monomeric guanine nucleotide-binding proteins, because GTPase activity of other members of the Ras superfamily is increased by a separate GAP molecule, which interacts with the effector region of the protein (17). Using chimeric proteins, we demonstrated that the GAP domain of ARD1 similarly interacts with the effector region of the ARF domain of ARD1 and thereby stimulates GTP hydrolysis (17).Nucleotide hydrolysis and product dissociation are both regulated steps in the GTPase cycle. Because their rates determine when and for how long the G protein is active, it is important to precisely understand these mechanisms. We reported that GDP␤S dissociation from p3 was faster than from ARD1 (18). Accordingly, in the presence of certain phospholipids (i.e. brain phosphatidylcholine plus phosphatidylinositol bisphosphate plus phosphatidylethanolamine or phosphatidylserine) more G...

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“…3). Therefore, involvement of the amino-terminal ␣-helix of ARF1 in membrane affinity, nucleotide-induced conformational change, and effector interaction has been suggested (33, 34).…”

Section: Table Imentioning

confidence: 99%

mentioning

confidence: 99%

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Characterization of a GDP Dissociation Inhibitory Region of ADP-ribosylation Factor Domain Protein ARD1

Vitale

Moss

Vaughan

1997

Journal of Biological Chemistry

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“…Nevertheless, COPI does interact with the inositol phosphates inositol 1,3,4,5-tetrakisphosphate and inositol hexakisphosphate (37). Finally, binding of ADP-ribosylation factor to membranes activates phospholipase D activity, an event that is likely to directly or indirectly affect COPI recruitment (16).…”

Section: Fig 3 ␤-Cop Pi Is Shifted By Alkaline Phosphatase Treatmentmentioning

confidence: 99%

“…The coatomer complex is a high molecular weight heterooligomer composed of seven proteins, ␣-COP (160 kDa), ␤-COP (110 kDa), ␤Ј-COP (102 kDa), ␥-COP (98 kDa), ␦-COP (61 kDa), ⑀-COP (35 kDa), and -COP (20 kDa), each present in equimolar amounts (13,14). Binding of coatomer to membranes is dependent on adp-RIBO-SYLATION FACTOR, a small myristoylated GTPase that is thought to bind GTP upon interaction with a membrane-associated guanine nucleotide exchange factor (15)(16)(17). Exchange of GDP for GTP facilitates coatomer binding by an as yet unknown mechanism that is sensitive to the drug brefeldin A (18).…”

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confidence: 99%

Biochemical Heterogeneity and Phosphorylation of Coatomer Subunits

Sheff¹,

Lowe²,

Kreis

et al. 1996

Journal of Biological Chemistry

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The coat protomer complex I (COPI) family of coat proteins are involved in the assembly of membrane-associated coats thought to mediate vesicular transport between the endoplasmic reticulum and the Golgi complex, between adjacent Golgi cisternae, and possibly in the endocytic pathway. We investigated whether this heterogeneity in the sites of COPI action might be reflected in biochemical heterogeneity of one or more COPI subunits. A simplified method was devised to purify the cytosolic COPI precursor complex, coatomer, from rat liver cytosol. The individual subunits were analyzed by high resolution two dimensional gel electrophoresis and mass spectroscopic analysis of tryptic peptides. Considerable charge heterogeneity was observed, particularly for the ␤-COP and ␦-COP subunits. The multiple species detected, however, did not appear to reflect the presence of distinct translation products but rather a significant degree of protein phosphorylation. The observed pI of ␤-COP was sensitive to alkaline phosphatase digestion. Moreover, isolation of coatomer from metabolically labeled tissue culture cells demonstrated directly that both ␤-COP and ␦-COP, but no other coatomer subunits, were serine-phosphorylated. COPI phosphorylation may regulate coatomer assembly, membrane recruitment, or the specificity of coatomerorganelle interaction.

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Golgi Apparatus

Warren¹

2002

Encyclopedia of Molecular Biology

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Structure and Function of ARF Proteins: Activators of Cholera Toxin and Critical Components of Intracellular Vesicular Transport Processes

Cited by 300 publications

References 52 publications

Characterization of a GDP Dissociation Inhibitory Region of ADP-ribosylation Factor Domain Protein ARD1

Characterization of a GDP Dissociation Inhibitory Region of ADP-ribosylation Factor Domain Protein ARD1

Biochemical Heterogeneity and Phosphorylation of Coatomer Subunits

Golgi Apparatus

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