ABC1, an ATP Binding Cassette Transporter Required for Phagocytosis of Apoptotic Cells, Generates a Regulated Anion Flux after Expression in Xenopus laevis Oocytes
Open Access
- 1 January 1997
- journal article
- Published by Elsevier BV in Journal of Biological Chemistry
- Vol. 272 (5), 2695-2699
- https://doi.org/10.1074/jbc.272.5.2695
Abstract
The ATP binding cassette transporter ABC1 is a 220-kDa glycoprotein expressed by macrophages and required for engulfment of cells undergoing programmed cell death. Since members of this family of proteins such as P-glycoprotein and cystic fibrosis transmembrane conductance regulator share the ability to transport anions, we have investigated the transport capability of ABC1 expressed in Xenopus oocytes using iodide efflux and voltage-clamp techniques. We report here that ABC1 generates an anion flux sensitive to glibenclamide, sulfobromophthalein, and blockers of anion transporters. The anion flux generated by ABC1 is up-regulated by orthovanadate, cAMP, protein kinase A, and okadaic acid. In other ABC transporters, mutating the conserved lysine in the nucleotide binding folds was found to severely reduce or abolish hydrolysis of ATP, which in turn altered the activity of the transporter. In ABC1, replacement of the conserved lysine 1892 in the Walker A motif of the second nucleotide binding fold increased the basal ionic flux, did not alter the pharmacological inhibitory profile, but abolished the response to orthovanadate and cAMP agonists. Therefore, we conclude that ABC1 is a cAMP-dependent and sulfonylurea-sensitive anion transporter.Keywords
This publication has 27 references indexed in Scilit:
- Altered Drug-stimulated ATPase Activity in Mutants of the Human Multidrug Resistance ProteinPublished by Elsevier BV ,1996
- The ABC of channel regulationCell, 1995
- The First Nucleotide Binding Fold of the Cystic Fibrosis Transmembrane Conductance Regulator Can Function as an Active ATPaseJournal of Biological Chemistry, 1995
- Functional Dissection of P-glycoprotein Nucleotide-binding Domains in Chimeric and Mutant ProteinsPublished by Elsevier BV ,1995
- Mutations in the Sulfonylurea Receptor Gene in Familial Persistent Hyperinsulinemic Hypoglycemia of InfancyScience, 1995
- Coupling of CFTR Cl− channel gating to an ATP hydrolysis cycleNeuron, 1994
- BIOCHEMISTRY OF MULTIDRUG RESISTANCE MEDIATED BY THE MULTIDRUG TRANSPORTERAnnual Review of Biochemistry, 1993
- ATPase activity of partially purified P-glycoprotein from multidrug-resistant Chinese hamster ovary cellsBiochimica et Biophysica Acta (BBA) - Biomembranes, 1992
- ATP‐dependent bacterial transporters and cystic fibrosis: analogy between channels and transportersThe FASEB Journal, 1992
- Identification of the Cystic Fibrosis Gene: Cloning and Characterization of Complementary DNAScience, 1989