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Human monocarboxylate transporter 2 (MCT2) is a high affinity pyruvate transporter
R Y Lin1, J C Vera, R S Chaganti
1Program of Molecular Pharmacology and Therapeutics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
The Journal of Biological Chemistry
|October 24, 1998
Summary
Researchers identified a new human pyruvate transporter, MCT2. This transporter shows high affinity for pyruvate and is highly expressed in cancer cells, suggesting a distinct role from MCT1 in human cells.
Area of Science:
- Cellular biology
- Molecular biology
- Biochemistry
Background:
- Monocarboxylate transporters (MCTs) mediate pyruvate and lactate transport in mammalian cells.
- Understanding specific MCT roles is crucial for cellular metabolism and disease research.
Purpose of the Study:
- To molecularly clone and characterize a novel human monocarboxylate transporter, MCT2.
- To investigate the kinetic properties, gene mapping, tissue distribution, and expression patterns of human MCT2.
- To compare MCT2 with MCT1 to elucidate their distinct biological roles.
Main Methods:
- Molecular cloning of human MCT2 cDNA.
- Analysis of cDNA length (1,907 bp) and encoded polypeptide (478 amino acids) with 12 predicted transmembrane domains.
- Gene mapping to chromosome 12q13 using fluorescence in situ hybridization.
- Kinetic analysis to determine transporter properties.
- Comparison of tissue distribution and RNA transcript variants of MCT1 and MCT2.
- Analysis of mRNA expression in normal tissues and cancer cell lines.
Main Results:
- Human MCT2 cDNA encodes a 478-amino acid protein with 12 transmembrane domains.
- Human MCT2 maps to chromosome 12q13.
- MCT2 exhibits high affinity for pyruvate (apparent Km of 25 microM), identifying it as a primary pyruvate transporter.
- MCT2 mRNA expression is restricted in normal tissues but widespread in cancer cell lines.
- Co-expression of MCT1 and MCT2 mRNA was observed in various human cancer cell lines.
Conclusions:
- Human MCT2 functions as a high-affinity pyruvate transporter.
- MCT2 expression is differentially regulated, with increased presence in neoplastic cells.
- Distinct biological roles for MCT1 and MCT2 are suggested by their differing tissue distribution and expression patterns.