A precursor form of human kidney gamma-glutamyl transferase in normal and cancerous tissues, and its possible post-translational modification.
We have found three molecular forms of human gamma-glutamyl transferase (GGT) in normal and renal cell carcinomatous tissues, and also have reported the marked differences in the sugar chains of GGTs between normal and cancerous tissues by serial lectin affinity chromatographies. In this study, the peptide maps of three purified GGTs (79 kDa, 50 kDa and 25 kDa) obtained by lysylendopeptidase digestion, the subcellular localization of GGTs, and the sugar chains of GGTs were compared between normal and cancerous tissues. According to the results, the total peptide bands of the digested 79 kDa component represented the sum of those of the digested 50 and 25 kDa components on 12.5% SDS-PAGE. In addition, C-terminal and N-terminal amino-acid sequences of the 79 kDa protein were the same as the sequences of light and heavy subunits, respectively, suggesting that the 79 kDa component is of the precursor form of the 50 kDa mature heavy and 25 kDa light subunits, respectively. On the other hand, the GGT activity in renal cell carcinomatous tissues was significantly increased in the microsomal fraction and decreased in the soluble fraction compared with that of normal tissues. Meanwhile, the sugar moiety of GGTs in the respective subcellular fractions was obviously different between normal and cancerous tissues. In particular, a reduced multiantennary complex type sugar chain and an elevated high-mannose or hybrid-type sugar chain in the microsomal fraction were observed in the GGT in cancerous tissues.
D000595:Amino Acid Sequence; D002292:Carcinoma, Renal Cell / Q000201:enzymology*; D002458:Cell Fractionation; D002846:Chromatography, Affinity; D010450:Endopeptidases / Q000378:metabolism; D004792:Enzyme Precursors / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D007680:Kidney Neoplasms / Q000201:enzymology*; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009844:Oligosaccharides / Q000737:chemistry; D010449:Peptide Mapping; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017421:Sequence Analysis; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis / Q000737:chemistry* / Q000378:metabolism
D004792:Enzyme Precursors; D009844:Oligosaccharides; D005723:gamma-Glutamyltransferase; D010450:Endopeptidases