Koike Koji, Deeley Roger G, Cole Susan P C
Cancer Research Laboratories, Queen's University, Kingston, Ont., Canada K7L 3N6.
Biochem Biophys Res Commun. 2004 Mar 12;315(3):719-25. doi: 10.1016/j.bbrc.2004.01.111.
Multidrug resistance in human tumour cells is often associated with increased expression of the 190kDa 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.
人类肿瘤细胞中的多药耐药性通常与190kDa多药耐药蛋白MRP1的表达增加有关，MRP1属于ATP结合盒转运蛋白超家族。MRP1也是许多有机阴离子的高效转运体。在本研究中，我们已将MRP1特异性鼠单克隆抗体（MAb）MRPm5的表位定位到位于该蛋白第三个跨膜结构域中连接跨膜螺旋13和14的胞质环（CL6）中的十肽（1063）FFERTPSGNL（1072）。据报道，MRP1胞质环中的几个氨基酸对其转运功能很重要；然而，MAb MRPm5并不抑制高亲和力底物白三烯C4的囊泡摄取。迄今为止描述的其他与MRP1反应的单克隆抗体均未定位到MRP1的CL6，这反过来增强了MAb MRPm5在该转运体临床和实验研究中的效用。
