Multidrug resistance protein. Identification of regions required for active transport of leukotriene C4.

The Journal of Biological Chemistry
M GaoR G Deeley

Abstract

Multidrug resistance protein (MRP) is a broad specificity, primary active transporter of organic anion conjugates that confers a multidrug resistance phenotype when transfected into drug-sensitive cells. The protein was the first example of a subgroup of the ATP-binding cassette superfamily whose members have three membrane-spanning domains (MSDs) and two nucleotide binding domains. The role(s) of the third MSD of MRP and its related transporters is not known. To begin to address this question, we examined the ability of various MRP fragments, expressed individually and in combination, to transport the MRP substrate, leukotriene C4 (LTC4). We found that elimination of the entire NH2-terminal MSD or just the first putative transmembrane helix, or substitution of the MSD with the comparable region of the functionally and structurally related transporter, the canalicular multispecific organic anion transporter (cMOAT/MRP2), had little effect on protein accumulation in the membrane. However, all three modifications decreased LTC4 transport activity by at least 90%. Transport activity could be reconstituted by co-expression of the NH2-terminal MSD with a fragment corresponding to the remainder of the MRP molecule, but this required ...Continue Reading

References

Jan 1, 1992·Annual Review of Cell Biology·C F Higgins
Jan 1, 1990·Annual Review of Cell Biology·S J Singer
Sep 1, 1989·Molecular and Cellular Biology·J E ChinI B Roninson
Sep 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·L BishopG F Ames
May 1, 1987·Proceedings of the National Academy of Sciences of the United States of America·K UedaI Pastan
Nov 1, 1981·Journal of Pharmacobio-dynamics·K YamaokaT Uno
Feb 1, 1995·Journal of Bioenergetics and Biomembranes·U A GermannM M Gottesman
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·M J AndrolewiczP Cresswell
Dec 20, 1994·Proceedings of the National Academy of Sciences of the United States of America·M MüllerP L Jansen
Sep 13, 1994·Proceedings of the National Academy of Sciences of the United States of America·G J ZamanH J Broxterman
Mar 1, 1994·European Journal of Biochemistry·I LeierD Keppler
May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·M A van KuijckP M Deen
May 24, 1996·The Journal of Biological Chemistry· Bakos EB Sarkadi
Jun 1, 1996·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·D W LoeS P Cole

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Citations

Jul 19, 2006·Pflügers Archiv : European journal of physiology·Anne T Nies, Dietrich Keppler
Aug 7, 2002·Biochemical and Biophysical Research Communications·Denise M WilkesGuillermo A Altenberg
Feb 10, 2010·Annals of Indian Academy of Neurology·Manna Jose, Sanjeev V Thomas
Dec 11, 1999·Proceedings of the Association of American Physicians·J M Drazen
Dec 27, 2005·FEBS Letters·Esther Biemans-OldehinkelBert Poolman
Jan 31, 2006·FEBS Letters·Annie Frelet, Markus Klein
Jan 3, 2006·FEBS Letters·Roger G Deeley, Susan P C Cole
Mar 16, 2007·Biochemical Pharmacology·Rémi-Martin LabergeElias Georges
Aug 11, 2001·Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy·Johan RenesMichael Müller
Nov 5, 2016·Biochimica Et Biophysica Acta. Biomembranes·Sven Marcel SchmittMichael Wiese
Oct 25, 2003·Oncogene·Gary D Kruh, Martin G Belinsky
Dec 8, 2004·The Journal of Biological Chemistry·Xiao-Qin RenShin-ichi Akiyama
Oct 3, 1999·The Journal of Biological Chemistry·K F Raab-GrahamC A Vandenberg
Jul 18, 2003·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Kenichi NunoyaRoger G Deeley
Nov 2, 2019·Molecular Carcinogenesis·Taylor C PeakGagan Deep

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