Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.

摘要: System L is a major nutrient transport system responsible for the of large neutral amino acids including several essential acids. We previously identified transporter (L-type acid 1: LAT1) subserving in C6 rat glioma cells and demonstrated that LAT1 requires 4F2 heavy chain (4F2hc) its functional expression. Since oncofetal expression was suggested liver, it has been proposed plays critical role cell growth proliferation. In present study, we have examined function human (hLAT1) tissues tumor lines. When expressed Xenopus oocytes with 4F2hc (h4F2hc), hLAT1 transports high affinity (K(m)= approximately 15- 50 microM) L-glutamine L-asparagine low 1.5- 2 mM). also D-amino such as D-leucine D-phenylalanine. addition, show accepts an acid-related anti-cancer agent melphalan. loaded intracellularly, L-leucine but not L-alanine are effluxed by extracellular substrates, confirming mediates exchange. mRNA highly fetal bone marrow, placenta, testis brain. found that, while all lines express messages, h4F2hc varied particularly leukemia Western blot analysis, confirmed to be linked each other via disulfide bond T24 bladder carcinoma cells. Finally, vitro translation, glycosylated protein even though N-glycosylation site predicted loop, consistent property classical light chain. The properties hLAT1/h4F2hc complex would support roles this providing cellular responses, distributing compounds.