Mapping of the MRPm5 epitope to the cytosolic region between transmembrane helices 13 and 14 in the drug and organic anion transporter, MRP1 (ABCC1)

被引:6
作者
Koike, K [1 ]
Deeley, RG [1 ]
Cole, SPC [1 ]
机构
[1] Queens Univ, Canc Res Labs, Kingston, ON K7L 3N6, Canada
基金
加拿大健康研究院;
关键词
multidrug; resistance; MRP1; organic anion transporter; monoclonal antibody; epitope mapping; cytoplasmic loop; membrane protein;
D O I
10.1016/j.bbrc.2004.01.111
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Multidrug resistance in human tumour cells is often associated with increased expression of the 190 kDa multidrug resistance protein, MRP1, that belongs to the ATP-binding cassette superfamily of transport proteins. MRP1 is also an efficient transporter of many organic anions. In the present study, we have mapped the epitope of the MRP1-specific murine monoclonal antibody (MAb) MRPm5 to the decapeptide (1063)FFERTPSGNL(1072) located in the cytoplasmic loop (CL6) linking transmembrane helices 13 and 14 in the third membrane spanning domain of the protein. Several amino acids in the cytoplasmic loops of MRP1 have been reported to be important for its transport function; nevertheless, MAb MRPm5 does not inhibit vesicular uptake of the high affinity substrate leukotriene C-4. None of the other MRP1-reactive MAbs described to date map to CL6 of MRP1 which in turn enhances the utility of MAb MRPm5 for both clinical and experimental investigations of this transporter. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:719 / 725
页数:7
相关论文
共 34 条
  • [1] Membrane topology and glycosylation of the human multidrug resistance-associated protein
    Bakos, E
    Hegedus, T
    Hollo, Z
    Welker, E
    Tusnady, GE
    Zaman, GJR
    Flens, MJ
    Varadi, A
    Sarkadi, B
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (21) : 12322 - 12326
  • [2] BATES SE, 2003, ABC PROTEINS BACTERI, P359
  • [3] Mammalian ABC transporters in health and disease
    Borst, P
    Elferink, RO
    [J]. ANNUAL REVIEW OF BIOCHEMISTRY, 2002, 71 : 537 - 592
  • [4] Molecular modeling correctly predicts the functional importance of Phe594 in transmembrane Helix 11 of the multidrug resistance protein, MRP1 (ABCC1)
    Campbell, JD
    Koike, K
    Moreau, C
    Sansom, MSP
    Deeley, RG
    Cole, SPC
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (01) : 463 - 468
  • [5] RETRACTED: Structure of MsbA from Vibrio cholera:: A multidrug resistance ABC transporter homolog in a closed conformation (Retracted Article. See vol 369, pg 596, 2007)
    Chang, G
    [J]. JOURNAL OF MOLECULAR BIOLOGY, 2003, 330 (02) : 419 - 430
  • [6] Cytoplasmic retraction of the amino terminus of human multidrug resistance protein 1
    Chen, Q
    Yang, YY
    Liu, Y
    Han, BG
    Zhang, JT
    [J]. BIOCHEMISTRY, 2002, 41 (29) : 9052 - 9062
  • [7] OVEREXPRESSION OF A TRANSPORTER GENE IN A MULTIDRUG-RESISTANT HUMAN LUNG-CANCER CELL-LINE
    COLE, SPC
    BHARDWAJ, G
    GERLACH, JH
    MACKIE, JE
    GRANT, CE
    ALMQUIST, KC
    STEWART, AJ
    KURZ, EU
    DUNCAN, AMV
    DEELEY, RG
    [J]. SCIENCE, 1992, 258 (5088) : 1650 - 1654
  • [8] A new monoclonal antibody, P2A8(6), that specifically recognizes a novel epitope on the multidrug resistance-associated protein 1 (MRP1), but not on MRP2 nor MRP3
    Connolly, L
    Moran, E
    Larkin, A
    Scheffer, G
    Scheper, R
    Sarkadi, B
    Kool, M
    Clynes, M
    [J]. HYBRIDOMA AND HYBRIDOMICS, 2001, 20 (5-6): : 333 - 341
  • [9] CUI L, 2001, ARCH BIOCH BIOPHYS, V392, P53
  • [10] The multidrug resistance protein is photoaffinity labeled by a quinoline-based drug at multiple sites
    Daoud, R
    Desneves, J
    Deady, LW
    Tilley, L
    Scheper, RJ
    Gros, P
    Georges, E
    [J]. BIOCHEMISTRY, 2000, 39 (20) : 6094 - 6102