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J Biol Chem, Vol. 274, Issue 17, 11455-11458, April 23, 1999
From the Department of Biochemistry, Institute of Basic Medical
Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575 Japan
Transport system
xc
found in plasma membrane of
cultured mammalian cells is an exchange agency for anionic amino acids
with high specificity for anionic form of cystine and glutamate. We have isolated cDNA encoding the transporter for system
xc from mouse activated macrophages
by expression in Xenopus oocytes. The expression of system
xc activity in oocytes required two
cDNA transcripts, and the sequence analysis revealed that one is
identical with the heavy chain of 4F2 cell surface antigen (4F2hc) and
the other is a novel protein of 502 amino acids with 12 putative
transmembrane domains. The latter protein, named xCT, showed a
significant homology with those recently reported to mediate cationic
or zwitterionic amino acid transport when co-expressed with 4F2hc. Thus
xCT is a new member of a family of amino acid transporters that form
heteromultimeric complex with 4F2hc, with a striking difference in
substrate specificity. The expression of system
xc was highly regulated, and
Northern blot analysis demonstrated that the expression of both 4F2hc
and xCT was enhanced in macrophages stimulated by lipopolysaccharide or
an electrophilic agent. However, the expression of xCT was more
directly correlated with the system xc activity.
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