ABCMdb

PMID: 15161912

Leslie EM, Haimeur A, Waalkes MP
Arsenic transport by the human multidrug resistance protein 1 (MRP1/ABCC1). Evidence that a tri-glutathione conjugate is required.
J Biol Chem. 2004 Jul 30;279(31):32700-8. Epub 2004 May 25., 2004-07-30 [PubMed]

Sentences

No. Mutations Sentence Comment

69 ABCC1 p.Lys332Leu ABCC1 p.Asp336Lys ABCC1 p.Lys347Asp ABCC1 p.Lys319Asp MRP1 and MRP2 Expression Vectors and Transfections in HEK293T Cells-The construction and expression of wild-type MRP1 (WT-MRP1), wild-type MRP2 (WT-MRP2), and the MRP1 mutants K332L, D336K, K319D, and K347D in HEK293T cells have been described previously (31, 35-37). Login to comment 204 ABCC1 p.Lys332Leu ABCC1 p.Asp336Lys ABCC1 p.Lys347Asp ABCC1 p.Lys319Asp To determine whether these amino acid residues are critical for transport of As(GS)3, transport assays were done using membrane vesicles prepared from HEK293T cells transfected with pcDNA3.1(-) (empty vector), WT-MRP1, D336K-MRP1, K332L-MRP1, K319D-MRP1, and K347D-MRP1 cDNAs. Login to comment 206 ABCC1 p.Lys332Leu ABCC1 p.Asp336Lys Consistent with the selective loss of LTC4 and GSH transport by K332L-MRP1 and the general loss of transport function by D336K-MRP1, these mutants also did not transport As(GS)3 (Fig. 8B). Login to comment 207 ABCC1 p.Lys347Asp ABCC1 p.Lys319Asp Despite the fact that K319D-MRP1 and K347D-MRP1 have a selectively decreased ability to transport GSH, these mutants transported As(GS)3 at levels similar to WT-MRP1. Login to comment 222 ABCC1 p.Lys332Leu ABCC1 p.Asp336Lys ABCC1 p.Lys347Asp ABCC1 p.Lys319Asp As(GS)3 transport by wild-type and mutant K332L, D336K, K319D, K347D-MRP1. Login to comment 223 ABCC1 p.Lys332Leu ABCC1 p.Asp336Lys ABCC1 p.Lys347Asp ABCC1 p.Lys319Asp A, membrane vesicles prepared from HEK293T cells transfected with empty vector (pcDNA3.1(-)), wild-type MRP1 (WT-MRP1), or mutant MRP1 (K332L-MRP1, D336K-MRP1, K319D-MRP1, or K347D-MRP1) were immunoblotted with the MRP1-specific mAb QCRL-1 as described under "Experimental Procedures." Login to comment