| http://purl.uniprot.org/citations/12682044 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/12682044 | http://www.w3.org/2000/01/rdf-schema#comment | "The human multidrug resistance protein MRP1 and its homolog, MRP2, are both thought to be involved in cancer drug resistance and the transport of a wide variety of organic anions, including the cysteinyl leukotriene C4 (LTC4) (Km = 0.1 and 1 microm). To determine which domain of these proteins is associated with substrate specificity and subcellular localization, we constructed various chimeric MRP1/MRP2 molecules and expressed them in polarized mammalian LLC-PK1 cells. We examined the kinetic properties of each chimeric protein by measuring LTC4 and methotrexate transport in inside-out membrane vesicles, sensitivity to an anticancer agent, etoposide, and subcellular localization by indirect immunofluorescence methods. The following results were determined in these studies: (i) when the NH2-proximal 108 amino acids of MRP2, including transmembrane (TM) helices 1-3, were exchanged with the corresponding region of MRP1, Km(LTC4) values of the chimera decreased approximately 4-fold and Km(methotrexate) values increased approximately 5-fold relative to those of wild-type MRP2 and MRP1, respectively, whereas resistance to etoposide increased approximately 3-fold; (ii) when the NH2-proximal region up to TM9 of MRP2 was exchanged with the corresponding region of MRP1, a further increase in etoposide resistance was observed, and subcellular localization moved from the apical to the lateral membrane; (iii) when two-thirds of MRP2 at the NH2 terminus were exchanged with the corresponding MRP1 region, the chimeric protein transported LTC4 with an efficiency comparable with that achieved by the wild-type MRP1; and (iv) exchange of the COOH-terminal 51 amino acids between MRP1 and MRP2 did not affect the localization of either of the proteins. These results provide a strong framework for further studies aimed at determining the precise domains of MRP1 and MRP2 with affinity for LTC4 and anticancer agents."xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m302868200"xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/author | "Nakamura T."xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/author | "Wada M."xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/author | "Uchiumi T."xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/author | "Konno T."xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/author | "Kuwano M."xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/author | "Ebihara T."xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/author | "Shirakusa T."xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/author | "Hisaeda K."xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/date | "2003"xsd:gYear |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/pages | "22908-22917"xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/title | "Identification of domains participating in the substrate specificity and subcellular localization of the multidrug resistance proteins MRP1 and MRP2."xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://purl.uniprot.org/core/volume | "278"xsd:string |
| http://purl.uniprot.org/citations/12682044 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/12682044 |
| http://purl.uniprot.org/citations/12682044 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/12682044 |
| http://purl.uniprot.org/uniprot/#_A0A0S2Z4R8-mappedCitation-12682044 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/12682044 |
| http://purl.uniprot.org/uniprot/#_Q15547-mappedCitation-12682044 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/12682044 |
| http://purl.uniprot.org/uniprot/#_A0A1V0E419-mappedCitation-12682044 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/12682044 |
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| http://purl.uniprot.org/uniprot/#_A0A1V0E3X4-mappedCitation-12682044 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/12682044 |
| http://purl.uniprot.org/uniprot/#_A0A1V0E3X6-mappedCitation-12682044 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/12682044 |