Human Lung Expresses Unique γ-Glutamyl Transpeptidase Transcripts

γ-Glutamyl transpeptidase (EC 2.3.2.2, γGT) is a membrane-bound ectoenzyme that plays an important role in the metabolism of glutathione. It is composed of two subunits, both of which are encoded by a common mRNA. We examined the expression of γGT in human lung tissue by Northern blot analysis and screening a cDNA library made from human lung poly(A)+RNA. Our results show that there are two γ GT mRNA populations in human lung tissue. We define these as group I (2.4 kb) and group II (≈1.2 kb) transcripts. In the present communication, we characterize the unique lung transcript. Sequence analysis of representative clones shows that group I transcripts are virtually identical to those previously isolated from liver and placenta but possess a unique 5' untranslated region. In marked contrast, group II transcripts appear to be human-lung-specific. Group II transcripts appear on Northern blots probed with full-length or 3'-biased γGT cDNA. Sequence analysis of group II clones shows them to be homologous with group I clones in the region that encodes the reading frame for the light chain; however, they possess a series of unique 5' untranslated regions, which suggests that they arise from lung-specific message processing. Additionally, ≈50% of the isolated group II clones contain 34 nt substitutions compared with the "wild-type" γGT transcripts. These data indicate that human lung expresses unique γGT transcripts of unknown function as well as the classical form. The abundant group II transcripts may encode part of a heterodimer related to γ GT or represent processed lung-specific pseudogenes.