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. 1986 Jul;39(1):79–87.

Human tissue-type plasminogen activator gene located near chromosomal breakpoint in myeloproliferative disorder.

T L Yang-Feng, G Opdenakker, G Volckaert, U Francke
PMCID: PMC1684028  PMID: 3092643

Abstract

Plasminogen activators (PA) convert the inactive proenzyme plasminogen into plasmin, which is involved in the process of fibrinolysis, tissue remodeling, and cell migration. There are two distinct forms of PA: urokinase (u-PA) and tissue-type plasminogen activator (t-PA). t-PA has higher affinity for fibrin and is the main form involved in thrombolysis. By in situ chromosomal hybridization and Southern blot analysis of somatic cell hybrid DNA, we have assigned the human t-PA gene to chromosome 8, bands 8p12----q11.2. We have detected a common EcoRI restriction fragment length polymorphism within the t-PA gene that thus provides a precisely localized highly informative marker for genetic linkage studies. The t-PA gene localization coincides with a translocation breakpoint observed in myeloproliferative disorders. Whereas leukemic cells usually secrete both types of PA, a correlation exists between acute myeloid leukemic cells that release only t-PA and failure to respond to chemotherapy.

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Selected References

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

  1. Ashino-Fuse H., Opdenakker G., Fuse A., Billiau A. Mechanism of the stimulatory effect of phorbol 12-myristate 13-acetate on cellular production of plasminogen activator. Proc Soc Exp Biol Med. 1984 Jun;176(2):109–118. doi: 10.3181/00379727-176-41849. [DOI] [PubMed] [Google Scholar]
  2. Bass E. B., Smith S. W., Jr, Stevenson R. E., Rosse W. F. Further evidence for location of the spherocytosis gene on chromosome 8. Ann Intern Med. 1983 Aug;99(2):192–193. doi: 10.7326/0003-4819-99-2-192. [DOI] [PubMed] [Google Scholar]
  3. Benham F. J., Spurr N., Povey S., Brinton B. T., Goodfellow P. N., Solomon E., Harris T. J. Assignment of tissue-type plasminogen activator to chromosome 8 in man and identification of a common restriction length polymorphism within the gene. Mol Biol Med. 1984 Aug;2(4):251–259. [PubMed] [Google Scholar]
  4. Bergmann S. R., Fox K. A., Ter-Pogossian M. M., Sobel B. E., Collen D. Clot-selective coronary thrombolysis with tissue-type plasminogen activator. Science. 1983 Jun 10;220(4602):1181–1183. doi: 10.1126/science.6602378. [DOI] [PubMed] [Google Scholar]
  5. Bányai L., Váradi A., Patthy L. Common evolutionary origin of the fibrin-binding structures of fibronectin and tissue-type plasminogen activator. FEBS Lett. 1983 Oct 31;163(1):37–41. doi: 10.1016/0014-5793(83)81157-0. [DOI] [PubMed] [Google Scholar]
  6. Collen D., Rijken D. C., Van Damme J., Billiau A. Purification of human tissue-type plasminogen activator in centigram quantities from human melanoma cell culture fluid and its conditioning for use in vivo. Thromb Haemost. 1982 Dec 27;48(3):294–296. [PubMed] [Google Scholar]
  7. Collen D., Topol E. J., Tiefenbrunn A. J., Gold H. K., Weisfeldt M. L., Sobel B. E., Leinbach R. C., Brinker J. A., Ludbrook P. A., Yasuda I. Coronary thrombolysis with recombinant human tissue-type plasminogen activator: a prospective, randomized, placebo-controlled trial. Circulation. 1984 Dec;70(6):1012–1017. doi: 10.1161/01.cir.70.6.1012. [DOI] [PubMed] [Google Scholar]
  8. Francke U., Busby N., Shaw D., Hansen S., Brown M. G. Intrachromosomal gene mapping in man: assignment of nucleoside phosphorylase to region 14cen leads to 14q21 by interspecific hybridization of cells with a t(X;14) (p22;q21) translocation. Somatic Cell Genet. 1976 Jan;2(1):27–40. doi: 10.1007/BF01539240. [DOI] [PubMed] [Google Scholar]
  9. Friedhoff F., Rajendra B., Moody R., Alapatt T. Novel reciprocal translocation between chromosomes 8 and 9 found in a patient with myeloproliferative disorder. Cancer Genet Cytogenet. 1983 Aug;9(4):391–394. doi: 10.1016/0165-4608(83)90088-2. [DOI] [PubMed] [Google Scholar]
  10. Heisterkamp N., Groffen J., Stephenson J. R., Spurr N. K., Goodfellow P. N., Solomon E., Carritt B., Bodmer W. F. Chromosomal localization of human cellular homologues of two viral oncogenes. Nature. 1982 Oct 21;299(5885):747–749. doi: 10.1038/299747a0. [DOI] [PubMed] [Google Scholar]
  11. Kimberling W. J., Fulbeck T., Dixon L., Lubs H. A. Localization of spherocytosis to chromosome 8 or 12 and report of a family with spherocytosis and a reciprocal translocation. Am J Hum Genet. 1975 Sep;27(5):586–594. [PMC free article] [PubMed] [Google Scholar]
  12. Kucherlapati R., Tepper R., Granelli-Piperno A., Reich E. Modulation and mapping of a human plasminogen activator by cell fusion. Cell. 1978 Dec;15(4):1331–1340. doi: 10.1016/0092-8674(78)90058-2. [DOI] [PubMed] [Google Scholar]
  13. Lewis J. P., Jenks H., Lazerson J. Philadelphia chromosome-negative chronic myelogenous leukemia in a child with t(8;9)(p11 or 12;q34). Am J Pediatr Hematol Oncol. 1983 Fall;5(3):265–269. [PubMed] [Google Scholar]
  14. Münke M., Kruse K., Goos M., Ropers H. H., Tolksdorf M. Genetic heterogeneity of the ichthyosis, hypogonadism, mental retardation, and epilepsy syndrome. Clinical and biochemical investigations on two patients with Rud syndrome and review of the literature. Eur J Pediatr. 1983 Oct;141(1):8–13. doi: 10.1007/BF00445661. [DOI] [PubMed] [Google Scholar]
  15. Opdenakker G., Ashino-Fuse H., Van Damme J., Billiau A., De Somer P. Effects of 12-O-tetradecanoylphorbol 13-acetate on the production of mRNAs for human tissue-type plasminogen activator. Eur J Biochem. 1983 Apr 5;131(3):481–487. doi: 10.1111/j.1432-1033.1983.tb07287.x. [DOI] [PubMed] [Google Scholar]
  16. Opdenakker G., Billiau A., Volckaert G., de Somer P. Determination of tissue-type plasminogen-activator mRNA in human and non-human cell lines by dot-blot hybridization. Biochem J. 1985 Oct 15;231(2):309–313. doi: 10.1042/bj2310309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Opdenakker G., Weening H., Collen D., Billiau A., de Somer P. Messenger RNA for human tissue plasminogen activator. Eur J Biochem. 1982 Jan;121(2):269–274. doi: 10.1111/j.1432-1033.1982.tb05781.x. [DOI] [PubMed] [Google Scholar]
  18. Peltz S. W., Katzenellenbogen B. S., Kneifel M. A., Mangel W. F. Plasminogen activators in tissues of the immature and estrogen-stimulated rat uterus and in uterine luminal fluid: characterization and properties. Endocrinology. 1983 Mar;112(3):890–897. doi: 10.1210/endo-112-3-890. [DOI] [PubMed] [Google Scholar]
  19. Pennica D., Holmes W. E., Kohr W. J., Harkins R. N., Vehar G. A., Ward C. A., Bennett W. F., Yelverton E., Seeburg P. H., Heyneker H. L. Cloning and expression of human tissue-type plasminogen activator cDNA in E. coli. Nature. 1983 Jan 20;301(5897):214–221. doi: 10.1038/301214a0. [DOI] [PubMed] [Google Scholar]
  20. Rajput B., Degen S. F., Reich E., Waller E. K., Axelrod J., Eddy R. L., Shows T. B. Chromosomal locations of human tissue plasminogen activator and urokinase genes. Science. 1985 Nov 8;230(4726):672–674. doi: 10.1126/science.3840278. [DOI] [PubMed] [Google Scholar]
  21. Rijken D. C., Collen D. Purification and characterization of the plasminogen activator secreted by human melanoma cells in culture. J Biol Chem. 1981 Jul 10;256(13):7035–7041. [PubMed] [Google Scholar]
  22. Scott R. W., Vogt T. F., Croke M. E., Tilghman S. M. Tissue-specific activation of a cloned alpha-fetoprotein gene during differentiation of a transfected embryonal carcinoma cell line. Nature. 1984 Aug 16;310(5978):562–567. doi: 10.1038/310562a0. [DOI] [PubMed] [Google Scholar]
  23. Southern E. Gel electrophoresis of restriction fragments. Methods Enzymol. 1979;68:152–176. doi: 10.1016/0076-6879(79)68011-4. [DOI] [PubMed] [Google Scholar]
  24. Van de Werf F., Bergmann S. R., Fox K. A., de Geest H., Hoyng C. F., Sobel B. E., Collen D. Coronary thrombolysis with intravenously administered human tissue-type plasminogen activator produced by recombinant DNA technology. Circulation. 1984 Mar;69(3):605–610. doi: 10.1161/01.cir.69.3.605. [DOI] [PubMed] [Google Scholar]
  25. Van de Werf F., Ludbrook P. A., Bergmann S. R., Tiefenbrunn A. J., Fox K. A., de Geest H., Verstraete M., Collen D., Sobel B. E. Coronary thrombolysis with tissue-type plasminogen activator in patients with evolving myocardial infarction. N Engl J Med. 1984 Mar 8;310(10):609–613. doi: 10.1056/NEJM198403083101001. [DOI] [PubMed] [Google Scholar]
  26. Wigler M., Weinstein I. B. Tumour promotor induces plasminogen activator. Nature. 1976 Jan 22;259(5540):232–233. doi: 10.1038/259232a0. [DOI] [PubMed] [Google Scholar]
  27. Wilson E. L., Jacobs P., Dowdle E. B. The secretion of plasminogen activators by human myeloid leukemic cells in vitro. Blood. 1983 Mar;61(3):568–574. [PubMed] [Google Scholar]
  28. Wilson E. L., Jacobs P., Oliver L. Plasminogen activator as a prognostic factor in hematological malignancies. Haematol Blood Transfus. 1985;29:197–199. doi: 10.1007/978-3-642-70385-0_45. [DOI] [PubMed] [Google Scholar]
  29. Yang-Feng T. L., Seeburg P. H., Francke U. Human luteinizing hormone-releasing hormone gene (LHRH) is located on short arm of chromosome 8 (region 8p11.2----p21). Somat Cell Mol Genet. 1986 Jan;12(1):95–100. doi: 10.1007/BF01560732. [DOI] [PubMed] [Google Scholar]
  30. de Martinville B., Wyman A. R., White R., Francke U. Assignment of first random restriction fragment length polymorphism (RFLP) locus ((D14S1) to a region of human chromosome 14. Am J Hum Genet. 1982 Mar;34(2):216–226. [PMC free article] [PubMed] [Google Scholar]

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