Human monocarboxylate transporter 2 (MCT2) is a high affinity pyruvate transporter

被引:168
作者
Lin, RY
Vera, JC
Chaganti, RSK
Golde, DW
机构
[1] Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol & Therapeut, New York, NY 10021 USA
[2] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA
关键词
D O I
10.1074/jbc.273.44.28959
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
The transport of pyruvate and lactate across cellular membranes is an essential process in mammalian cells and is mediated by the H+/monocarboxylate transporters (MCTs). We have molecularly cloned and characterized a novel human monocarboxylate transporter, MCT2. The cDNA is 1,907 base pairs long and encodes a polypeptide of 478 amino acids with 12 predicted transmembrane domains. Human MCT2 is the product of a single gene that mapped to chromosome 12q13 by fluorescence in situ hybridization, The kinetic properties of human MCT2 fulfill the criteria to establish it as a H(+/)monocarboxylate transporter; however, the unique biochemical feature of human MCT2 is its high affinity for the transport of pyruvate (apparent K-m of 25 mu M), implying that it is a primary pyruvate transporter in man. Comparison of human MCT1 and MCT2 with regard to tissue distribution and RNA transcript variants disclosed substantial differences. Human MCT2 mRNA expression was restricted in normal human tissues but widely expressed in cancer cell lines, suggesting that MCT2 may be pre-translationally regulated in neoplasia. We found co-expression of human MCT1 and MCT2 at the mRNA level in human cancer cell lines, including the hematopoietic lineages HL60, K562, MOLT-4, and Burkitt's lymphoma Raji, and solid tumor cells such as SW480, A549, and G361, These findings suggest that the two monocarboxylate transporters, MCT1 and MCT2, have distinct biological roles.
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页码:28959 / 28965
页数:7
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