Human lymphocyte methionine adenosyltransferase (HuLy MAT) consists of heterologous subunits ␣ and ␤. The cDNA sequence of the ␣ subunit of HuLy MAT from Jurkat leukemic T cells was identical to that of the human kidney ␣ subunit and highly homologous to the sequence of the extrahepatic MAT from other sources. The 3-untranslated sequence was found to be highly conserved, suggesting that it may be important in regulating the expression of MAT. The extrahepatic ␣ subunit of MAT was found to be

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... ressed also in human liver, and no differences were found in the sequence of the ␣ subunit from normal and malignant T cells. The sequence of two unspliced introns found in the cDNA clones from the Jurkat library enabled us to isolate genomic clones harboring the human extrahepatic ␣ subunit gene and to localize it to the centromere on chromosome arm 2p, an area that corresponds to band 2p11.2. Expression of the ␣ subunit cDNA in Escherichia coli yielded two peptides with the immunoreactivity and mobilities of authentic ␣/␣ subunits from HuLy. The K m of the recombinant ␣ subunit was 80 M, which is 20-fold higher than found for the (␣␣) x ␤ y holoenzyme purified from leukemic lymphocytes and 4 -10-fold higher than found for the normal lymphocyte enzyme. The data suggest that the ␣/␣ subunits mediate the enzyme catalytic activity and that the ␤ subunit may be a regulatory subunit of extrahepatic MAT.