title: Signalling via ADP-ribosylation factor 6 lies downstream of phosphatidylinositide 3-kinase.
abstract: ADP-ribosylation factor (ARF) 6 regulates plasma membrane trafficking and cortical actin formation by cycling between inactive GDP and active GTP-bound conformations. Here we show that agonist stimulation of phosphatidylinositide 3-kinase (PI 3-kinase) activates a pathway that leads to ARF6 activation. We also describe experiments that propose a central role in this pathway for the PI 3-kinase-dependent plasma membrane recruitment of the cytohesin-1 family of PtdIns(3,4,5)P(3)-binding ARF-exchange factors.
authors.affiliation: Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, U.K.
authors.forename: K
authors.initials: K
authors.lastname: Venkateswarlu
authors.forename: P J
authors.initials: PJ
authors.lastname: Cullen
mesh_terms: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism / Q000648:ultrastructure; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000730:Androstadienes / Q000494:pharmacology; D020126:Brefeldin A / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002867:Chromones / Q000494:pharmacology; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D020662:Guanine Nucleotide Exchange Factors; D006153:Guanosine Diphosphate / Q000378:metabolism; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D009025:Morpholines / Q000494:pharmacology; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013347:Subcellular Fractions; D000077191:Wortmannin
chemical_list: D000089982:ADP-Ribosylation Factor 6; D020727:ADP-Ribosylation Factors; D000199:Actins; D000730:Androstadienes; D020126:Brefeldin A; D015815:Cell Adhesion Molecules; D002867:Chromones; D016895:Culture Media, Serum-Free; D004791:Enzyme Inhibitors; D004815:Epidermal Growth Factor; D049452:Green Fluorescent Proteins; D020662:Guanine Nucleotide Exchange Factors; D006153:Guanosine Diphosphate; D008164:Luminescent Proteins; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D018129:Phosphatidylinositol Phosphates; D011994:Recombinant Proteins; D000077191:Wortmannin; C100723:cytohesin-1; C060974:phosphatidylinositol 3,4,5-triphosphate; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C000715348:ARF6 protein, human