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. 1993 Aug 15;90(16):7461–7465. doi: 10.1073/pnas.90.16.7461

Human lung expresses unique gamma-glutamyl transpeptidase transcripts.

L A Wetmore 1, C Gerard 1, J M Drazen 1
PMCID: PMC47161  PMID: 7689219

Abstract

gamma-Glutamyl transpeptidase (EC 2.3.2.2, gamma GT) 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 gamma GT 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 gamma GT mRNA populations in human lung tissue. We define these as group I (2.4 kb) and group II (approximately 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 gamma GT 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, approximately 50% of the isolated group II clones contain 34 nt substitutions compared with the "wild-type" gamma GT transcripts. These data indicate that human lung expresses unique gamma GT transcripts of unknown function as well as the classical form. The abundant group II transcripts may encode part of a heterodimer related to gamma GT or represent processed lung-specific pseudogenes.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Altman R. A., Hughey R. P. The identification of two subcellular sites for cleavage of gamma-glutamyltranspeptidase propeptide. Biochem Int. 1986 Dec;13(6):1009–1017. [PubMed] [Google Scholar]
  2. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
  5. Bulle F., Mattei M. G., Siegrist S., Pawlak A., Passage E., Chobert M. N., Laperche Y., Guellaën G. Assignment of the human gamma-glutamyl transferase gene to the long arm of chromosome 22. Hum Genet. 1987 Jul;76(3):283–286. doi: 10.1007/BF00283624. [DOI] [PubMed] [Google Scholar]
  6. Cantin A. M., North S. L., Hubbard R. C., Crystal R. G. Normal alveolar epithelial lining fluid contains high levels of glutathione. J Appl Physiol (1985) 1987 Jul;63(1):152–157. doi: 10.1152/jappl.1987.63.1.152. [DOI] [PubMed] [Google Scholar]
  7. Capraro M. A., Hughey R. P. Processing of the propeptide form of rat renal gamma-glutamyltranspeptidase. FEBS Lett. 1983 Jun 27;157(1):139–143. doi: 10.1016/0014-5793(83)81132-6. [DOI] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Curthoys N. P. Role of gamma-glutamyltranspeptidase in the renal metabolism of glutathione. Miner Electrolyte Metab. 1983;9(4-6):236–245. [PubMed] [Google Scholar]
  10. Dinsdale D., Green J. A., Manson M. M., Lee M. J. The ultrastructural immunolocalization of gamma-glutamyltranspeptidase in rat lung: correlation with the histochemical demonstration of enzyme activity. Histochem J. 1992 Mar;24(3):144–152. doi: 10.1007/BF01047464. [DOI] [PubMed] [Google Scholar]
  11. Finidori J., Laperche Y., Haguenauer-Tsapis R., Barouki R., Guellaen G., Hanoune J. In vitro biosynthesis and membrane insertion of gamma-glutamyl transpeptidase. J Biol Chem. 1984 Apr 25;259(8):4687–4690. [PubMed] [Google Scholar]
  12. Gerard N. P., Eddy R. L., Jr, Shows T. B., Gerard C. The human neurokinin A (substance K) receptor. Molecular cloning of the gene, chromosome localization, and isolation of cDNA from tracheal and gastric tissues. J Biol Chem. 1990 Nov 25;265(33):20455–20462. [PubMed] [Google Scholar]
  13. Gerard N. P., Garraway L. A., Eddy R. L., Jr, Shows T. B., Iijima H., Paquet J. L., Gerard C. Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones. Biochemistry. 1991 Nov 5;30(44):10640–10646. doi: 10.1021/bi00108a006. [DOI] [PubMed] [Google Scholar]
  14. Gerard N. P., Garraway L. A., Eddy R. L., Jr, Shows T. B., Iijima H., Paquet J. L., Gerard C. Human substance P receptor (NK-1): organization of the gene, chromosome localization, and functional expression of cDNA clones. Biochemistry. 1991 Nov 5;30(44):10640–10646. doi: 10.1021/bi00108a006. [DOI] [PubMed] [Google Scholar]
  15. Gerard N. P., Gerard C. The chemotactic receptor for human C5a anaphylatoxin. Nature. 1991 Feb 14;349(6310):614–617. doi: 10.1038/349614a0. [DOI] [PubMed] [Google Scholar]
  16. Goodspeed D. C., Dunn T. J., Miller C. D., Pitot H. C. Human gamma-glutamyl transpeptidase cDNA: comparison of hepatoma and kidney mRNA in the human and rat. Gene. 1989 Mar 15;76(1):1–9. doi: 10.1016/0378-1119(89)90002-4. [DOI] [PubMed] [Google Scholar]
  17. Matsuda Y., Tsuji A., Katunuma N. Studies on the structure of gamma-glutamyltranspeptidase. III. Evidence that the amino terminus of the heavy subunit is the membrane binding segment. J Biochem. 1983 May;93(5):1427–1433. doi: 10.1093/oxfordjournals.jbchem.a134278. [DOI] [PubMed] [Google Scholar]
  18. Meister A., Anderson M. E. Glutathione. Annu Rev Biochem. 1983;52:711–760. doi: 10.1146/annurev.bi.52.070183.003431. [DOI] [PubMed] [Google Scholar]
  19. Nash B., Tate S. S. In vitro translation and processing of rat kidney gamma-glutamyl transpeptidase. J Biol Chem. 1984 Jan 10;259(1):678–685. [PubMed] [Google Scholar]
  20. Orning L., Hammarström S., Samuelsson B. Leukotriene D: a slow reacting substance from rat basophilic leukemia cells. Proc Natl Acad Sci U S A. 1980 Apr;77(4):2014–2017. doi: 10.1073/pnas.77.4.2014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pawlak A., Cohen E. H., Octave J. N., Schweickhardt R., Wu S. J., Bulle F., Chikhi N., Baik J. H., Siegrist S., Guellaën G. An alternatively processed mRNA specific for gamma-glutamyl transpeptidase in human tissues. J Biol Chem. 1990 Feb 25;265(6):3256–3262. [PubMed] [Google Scholar]
  22. Pawlak A., Lahuna O., Bulle F., Suzuki A., Ferry N., Siegrist S., Chikhi N., Chobert M. N., Guellaen G., Laperche Y. gamma-Glutamyl transpeptidase: a single copy gene in the rat and a multigene family in the human genome. J Biol Chem. 1988 Jul 15;263(20):9913–9916. [PubMed] [Google Scholar]
  23. Pawlak A., Wu S. J., Bulle F., Suzuki A., Chikhi N., Ferry N., Baik J. H., Siegrist S., Guellaën G. Different gamma-glutamyl transpeptidase mRNAs are expressed in human liver and kidney. Biochem Biophys Res Commun. 1989 Oct 31;164(2):912–918. doi: 10.1016/0006-291x(89)91545-3. [DOI] [PubMed] [Google Scholar]
  24. Rajpert-De Meyts E., Heisterkamp N., Groffen J. Cloning and nucleotide sequence of human gamma-glutamyl transpeptidase. Proc Natl Acad Sci U S A. 1988 Dec;85(23):8840–8844. doi: 10.1073/pnas.85.23.8840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sakamuro D., Yamazoe M., Matsuda Y., Kangawa K., Taniguchi N., Matsuo H., Yoshikawa H., Ogasawara N. The primary structure of human gamma-glutamyl transpeptidase. Gene. 1988 Dec 15;73(1):1–9. doi: 10.1016/0378-1119(88)90307-1. [DOI] [PubMed] [Google Scholar]
  26. Stole E., Meister A. Interaction of gamma-glutamyl transpeptidase with glutathione involves specific arginine and lysine residues of the heavy subunit. J Biol Chem. 1991 Sep 25;266(27):17850–17857. [PubMed] [Google Scholar]
  27. Stole E., Seddon A. P., Wellner D., Meister A. Identification of a highly reactive threonine residue at the active site of gamma-glutamyl transpeptidase. Proc Natl Acad Sci U S A. 1990 Mar;87(5):1706–1709. doi: 10.1073/pnas.87.5.1706. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tate S. S., Meister A. gamma-Glutamyl transpeptidase: catalytic, structural and functional aspects. Mol Cell Biochem. 1981 Sep 25;39:357–368. doi: 10.1007/BF00232585. [DOI] [PubMed] [Google Scholar]
  29. Wetmore L. A., Gerard N. P., Herron D. K., Bollinger N. G., Baker S. R., Feldman H. A., Drazen J. M. Leukotriene receptor on U-937 cells: discriminatory responses to leukotrienes C4 and D4. Am J Physiol. 1991 Aug;261(2 Pt 1):L164–L171. doi: 10.1152/ajplung.1991.261.2.L164. [DOI] [PubMed] [Google Scholar]
  30. Wetmore L. A., Gerard N. P., Herron D. K., Bollinger N. G., Baker S. R., Feldman H. A., Drazen J. M. Leukotriene receptor on U-937 cells: discriminatory responses to leukotrienes C4 and D4. Am J Physiol. 1991 Aug;261(2 Pt 1):L164–L171. doi: 10.1152/ajplung.1991.261.2.L164. [DOI] [PubMed] [Google Scholar]

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