title: Association of a phosphatidylinositol-specific 3-kinase with a human trans-Golgi network resident protein.
abstract: The eukaryotic trans-Golgi network (TGN) is a key site for the formation of transport vesicles destined for different intracellular compartments [1]. A key marker for the mammalian TGN is TGN38/46 [2]. This integral membrane glycoprotein cycles between the TGN and the cell surface and is implicated in recruitment of cytosolic factors and regulation of at least one type of vesicle formation at the mammalian TGN [2] [3]. In this study, we have identified a phosphatidylinositol (PtdIns)-specific 3-kinase activity associated with the human orthologue (TGN46), which is sensitive to lipid kinase inhibitors. Treatment of HeLa cells with low levels of these inhibitors reveals subtle morphological changes in TGN46-positive compartments. Our findings suggest a role for PtdIns 3-kinases and presumably for the product, PtdIns 3-phosphate (PtdIns3P), in the formation of secretory transport vesicles by mechanisms conserved in yeast and mammals.
authors.affiliation: Department of Biochemistry, Medical Sciences Institute, University of Dundee, Dundee DD1 4HN, UK.
authors.forename: D M
authors.initials: DM
authors.lastname: Hickinson
authors.forename: J M
authors.initials: JM
authors.lastname: Lucocq
authors.forename: M C
authors.initials: MC
authors.lastname: Towler
authors.forename: S
authors.initials: S
authors.lastname: Clough
authors.forename: J
authors.initials: J
authors.lastname: James
authors.forename: S R
authors.initials: SR
authors.lastname: James
authors.forename: C P
authors.initials: CP
authors.lastname: Downes
authors.forename: S
authors.initials: S
authors.lastname: Ponnambalam
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D002867:Chromones / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006023:Glycoproteins; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008274:Magnesium / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009025:Morpholines; D010716:Phosphatidylinositols; C072237:TGOLN2 protein, human; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D008274:Magnesium; D000077191:Wortmannin