title: Protein tyrosine phosphatase inhibition down-regulates ligand-induced ABCA1 expression.
abstract: OBJECTIVE
  ATP-binding cassette transporter (ABC)-A1 is an important protein of cholesterol homoeostasis and atherosclerosis as it is the major lipid transporter responsible for the export of cholesterol from cells. Many studies have examined kinase regulation of ABCA1 expression. In contrast, very little is known about whether dephosphorylation events play a role in ABCA1 expression. In this study, we explored the involvement of phosphatases in the regulation of ABCA1 expression.
  
  
  RESULTS
  We observed that general protein tyrosine phosphatase inhibitors ablated ABCA1 protein and mRNA when stimulated with synthetic ligands. This effect is transcriptional, and appears to involve the nuclear receptor, retinoid X receptor (RXR).
  
  
  CONCLUSIONS
  Our data demonstrate that inhibition of protein tyrosine phosphatases down-regulates ABCA1 expression, indicating a new level of regulation of a key protein in cholesterol export.
authors.affiliation: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia.
authors.forename: Winnie
authors.initials: W
authors.lastname: Luu
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Sharpe
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Brown
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008024:Ligands; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D047488:Retinoid X Receptors / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D004791:Enzyme Inhibitors; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D012333:RNA, Messenger; D047488:Retinoid X Receptors; D017027:Protein Tyrosine Phosphatases