Skip to main content
NCBI home page
The Journal of Cell Biology logoLink to The Journal of Cell Biology
. 1991 Dec 2;115(6):1763–1771. doi: 10.1083/jcb.115.6.1763

Two alternatively spliced mouse urokinase receptor mRNAs with different histological localization in the gastrointestinal tract

PMCID: PMC2289218  PMID: 1661735

Abstract

Two mouse urokinase-type plasminogen activator receptor (muPAR) cDNAs were isolated: muPAR1 is homologous to the human urokinase-type plasminogen activator receptor while muPAR2 codes for a 199 residue protein sharing the first 133 residues with muPAR1. Mouse genomic DNA sequencing indicates that the two different mRNAs arise by alternative splicing. In situ hybridization showed differential expression of the two mRNAs in mouse gastric mucosa. muPAR1 mRNA is located in luminal epithelial cells situated close to urokinase-type plasminogen activator- producing connective tissue cells of the lamina propria, pointing to plasmin generation controlled by the cooperation of different cells that may play a role in the release of gastric epithelial cells. muPAR2 mRNA is expressed in the basal epithelial cells, and the deduced protein sequence includes the receptor ligand binding domain, but omits the region involved in glycolipid-mediated membrane anchoring, suggesting that muPAR2 may code for a secreted uPA binding protein.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Andreasen P. A., Georg B., Lund L. R., Riccio A., Stacey S. N. Plasminogen activator inhibitors: hormonally regulated serpins. Mol Cell Endocrinol. 1990 Jan 2;68(1):1–19. doi: 10.1016/0303-7207(90)90164-4. [DOI] [PubMed] [Google Scholar]
  2. Andreasen P. A., Kristensen P., Lund L. R., Danø K. Urokinase-type plasminogen activator is increased in the involuting ventral prostate of castrated rats. Endocrinology. 1990 May;126(5):2567–2576. doi: 10.1210/endo-126-5-2567. [DOI] [PubMed] [Google Scholar]
  3. Appella E., Robinson E. A., Ullrich S. J., Stoppelli M. P., Corti A., Cassani G., Blasi F. The receptor-binding sequence of urokinase. A biological function for the growth-factor module of proteases. J Biol Chem. 1987 Apr 5;262(10):4437–4440. [PubMed] [Google Scholar]
  4. Baumbach W. R., Horner D. L., Logan J. S. The growth hormone-binding protein in rat serum is an alternatively spliced form of the rat growth hormone receptor. Genes Dev. 1989 Aug;3(8):1199–1205. doi: 10.1101/gad.3.8.1199. [DOI] [PubMed] [Google Scholar]
  5. Behrendt N., Ploug M., Patthy L., Houen G., Blasi F., Danø K. The ligand-binding domain of the cell surface receptor for urokinase-type plasminogen activator. J Biol Chem. 1991 Apr 25;266(12):7842–7847. [PubMed] [Google Scholar]
  6. Behrendt N., Rønne E., Ploug M., Petri T., Løber D., Nielsen L. S., Schleuning W. D., Blasi F., Appella E., Danø K. The human receptor for urokinase plasminogen activator. NH2-terminal amino acid sequence and glycosylation variants. J Biol Chem. 1990 Apr 15;265(11):6453–6460. [PubMed] [Google Scholar]
  7. Berger J., Howard A. D., Brink L., Gerber L., Hauber J., Cullen B. R., Udenfriend S. COOH-terminal requirements for the correct processing of a phosphatidylinositol-glycan anchored membrane protein. J Biol Chem. 1988 Jul 15;263(20):10016–10021. [PubMed] [Google Scholar]
  8. Bergman B. L., Scott R. W., Bajpai A., Watts S., Baker J. B. Inhibition of tumor-cell-mediated extracellular matrix destruction by a fibroblast proteinase inhibitor, protease nexin I. Proc Natl Acad Sci U S A. 1986 Feb;83(4):996–1000. doi: 10.1073/pnas.83.4.996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Blasi F., Vassalli J. D., Danø K. Urokinase-type plasminogen activator: proenzyme, receptor, and inhibitors. J Cell Biol. 1987 Apr;104(4):801–804. doi: 10.1083/jcb.104.4.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Breitbart R. E., Andreadis A., Nadal-Ginard B. Alternative splicing: a ubiquitous mechanism for the generation of multiple protein isoforms from single genes. Annu Rev Biochem. 1987;56:467–495. doi: 10.1146/annurev.bi.56.070187.002343. [DOI] [PubMed] [Google Scholar]
  11. Caras I. W., Weddell G. N., Williams S. R. Analysis of the signal for attachment of a glycophospholipid membrane anchor. J Cell Biol. 1989 Apr;108(4):1387–1396. doi: 10.1083/jcb.108.4.1387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  13. Danø K., Andreasen P. A., Grøndahl-Hansen J., Kristensen P., Nielsen L. S., Skriver L. Plasminogen activators, tissue degradation, and cancer. Adv Cancer Res. 1985;44:139–266. doi: 10.1016/s0065-230x(08)60028-7. [DOI] [PubMed] [Google Scholar]
  14. Danø K., Moller V., Ossowski L., Nielsen L. S. Purification and characterization of a plasminogen activator from mouse cells transformed by an oncogenic virus. Biochim Biophys Acta. 1980 Jun 13;613(2):542–555. doi: 10.1016/0005-2744(80)90110-2. [DOI] [PubMed] [Google Scholar]
  15. Danø K., Reich E. Serine enzymes released by cultured neoplastic cells. J Exp Med. 1978 Mar 1;147(3):745–757. doi: 10.1084/jem.147.3.745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Devereux J., Haeberli P., Smithies O. A comprehensive set of sequence analysis programs for the VAX. Nucleic Acids Res. 1984 Jan 11;12(1 Pt 1):387–395. doi: 10.1093/nar/12.1part1.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Ellis V., Scully M. F., Kakkar V. V. Plasminogen activation initiated by single-chain urokinase-type plasminogen activator. Potentiation by U937 monocytes. J Biol Chem. 1989 Feb 5;264(4):2185–2188. [PubMed] [Google Scholar]
  18. Ellis V., Wun T. C., Behrendt N., Rønne E., Danø K. Inhibition of receptor-bound urokinase by plasminogen-activator inhibitors. J Biol Chem. 1990 Jun 15;265(17):9904–9908. [PubMed] [Google Scholar]
  19. Estreicher A., Mühlhauser J., Carpentier J. L., Orci L., Vassalli J. D. The receptor for urokinase type plasminogen activator polarizes expression of the protease to the leading edge of migrating monocytes and promotes degradation of enzyme inhibitor complexes. J Cell Biol. 1990 Aug;111(2):783–792. doi: 10.1083/jcb.111.2.783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Estreicher A., Wohlwend A., Belin D., Schleuning W. D., Vassalli J. D. Characterization of the cellular binding site for the urokinase-type plasminogen activator. J Biol Chem. 1989 Jan 15;264(2):1180–1189. [PubMed] [Google Scholar]
  21. Ferguson M. A., Williams A. F. Cell-surface anchoring of proteins via glycosyl-phosphatidylinositol structures. Annu Rev Biochem. 1988;57:285–320. doi: 10.1146/annurev.bi.57.070188.001441. [DOI] [PubMed] [Google Scholar]
  22. Gower H. J., Barton C. H., Elsom V. L., Thompson J., Moore S. E., Dickson G., Walsh F. S. Alternative splicing generates a secreted form of N-CAM in muscle and brain. Cell. 1988 Dec 23;55(6):955–964. doi: 10.1016/0092-8674(88)90241-3. [DOI] [PubMed] [Google Scholar]
  23. Grøndahl-Hansen J., Lund L. R., Ralfkiaer E., Ottevanger V., Danø K. Urokinase- and tissue-type plasminogen activators in keratinocytes during wound reepithelialization in vivo. J Invest Dermatol. 1988 Jun;90(6):790–795. doi: 10.1111/1523-1747.ep12461511. [DOI] [PubMed] [Google Scholar]
  24. Grøndahl-Hansen J., Ralfkiaer E., Kirkeby L. T., Kristensen P., Lund L. R., Danø K. Localization of urokinase-type plasminogen activator in stromal cells in adenocarcinomas of the colon in humans. Am J Pathol. 1991 Jan;138(1):111–117. [PMC free article] [PubMed] [Google Scholar]
  25. Huarte J., Belin D., Bosco D., Sappino A. P., Vassalli J. D. Plasminogen activator and mouse spermatozoa: urokinase synthesis in the male genital tract and binding of the enzyme to the sperm cell surface. J Cell Biol. 1987 May;104(5):1281–1289. doi: 10.1083/jcb.104.5.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Hébert C. A., Baker J. B. Linkage of extracellular plasminogen activator to the fibroblast cytoskeleton: colocalization of cell surface urokinase with vinculin. J Cell Biol. 1988 Apr;106(4):1241–1247. doi: 10.1083/jcb.106.4.1241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kristensen P., Eriksen J., Danø K. Localization of urokinase-type plasminogen activator messenger RNA in the normal mouse by in situ hybridization. J Histochem Cytochem. 1991 Mar;39(3):341–349. doi: 10.1177/39.3.1899685. [DOI] [PubMed] [Google Scholar]
  28. Kristensen P., Pyke C., Lund L. R., Andreasen P. A., Danø K. Plasminogen activator inhibitor-type 1 in Lewis lung carcinoma. Histochemistry. 1990;93(6):559–566. doi: 10.1007/BF00272198. [DOI] [PubMed] [Google Scholar]
  29. LeClair K. P., Palfree R. G., Flood P. M., Hammerling U., Bothwell A. Isolation of a murine Ly-6 cDNA reveals a new multigene family. EMBO J. 1986 Dec 1;5(12):3227–3234. doi: 10.1002/j.1460-2075.1986.tb04633.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Micanovic R., Bailey C. A., Brink L., Gerber L., Pan Y. C., Hulmes J. D., Udenfriend S. Aspartic acid-484 of nascent placental alkaline phosphatase condenses with a phosphatidylinositol glycan to become the carboxyl terminus of the mature enzyme. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1398–1402. doi: 10.1073/pnas.85.5.1398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Mignatti P., Robbins E., Rifkin D. B. Tumor invasion through the human amniotic membrane: requirement for a proteinase cascade. Cell. 1986 Nov 21;47(4):487–498. doi: 10.1016/0092-8674(86)90613-6. [DOI] [PubMed] [Google Scholar]
  32. Nielsen L. S., Kellerman G. M., Behrendt N., Picone R., Danø K., Blasi F. A 55,000-60,000 Mr receptor protein for urokinase-type plasminogen activator. Identification in human tumor cell lines and partial purification. J Biol Chem. 1988 Feb 15;263(5):2358–2363. [PubMed] [Google Scholar]
  33. Ossowski L., Biegel D., Reich E. Mammary plasminogen activator: correlation with involution, hormonal modulation and comparison between normal and neoplastic tissue. Cell. 1979 Apr;16(4):929–940. doi: 10.1016/0092-8674(79)90108-9. [DOI] [PubMed] [Google Scholar]
  34. Ossowski L., Reich E. Antibodies to plasminogen activator inhibit human tumor metastasis. Cell. 1983 Dec;35(3 Pt 2):611–619. doi: 10.1016/0092-8674(83)90093-4. [DOI] [PubMed] [Google Scholar]
  35. Palfree R. G., LeClair K. P., Bothwell A., Hämmerling U. cDNA characterization of an Ly-6.2 gene expressed in BW5147 tumor cells. Immunogenetics. 1987;26(6):389–391. doi: 10.1007/BF00343712. [DOI] [PubMed] [Google Scholar]
  36. Palfree R. G., Sirlin S., Dumont F. J., Hämmerling U. N-terminal and cDNA characterization of murine lymphocyte antigen Ly-6C.2. J Immunol. 1988 Jan 1;140(1):305–310. [PubMed] [Google Scholar]
  37. Pearson W. R., Lipman D. J. Improved tools for biological sequence comparison. Proc Natl Acad Sci U S A. 1988 Apr;85(8):2444–2448. doi: 10.1073/pnas.85.8.2444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Petch L. A., Harris J., Raymond V. W., Blasband A., Lee D. C., Earp H. S. A truncated, secreted form of the epidermal growth factor receptor is encoded by an alternatively spliced transcript in normal rat tissue. Mol Cell Biol. 1990 Jun;10(6):2973–2982. doi: 10.1128/mcb.10.6.2973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Ploug M., Rønne E., Behrendt N., Jensen A. L., Blasi F., Danø K. Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol. J Biol Chem. 1991 Jan 25;266(3):1926–1933. [PubMed] [Google Scholar]
  40. Plow E. F., Freaney D. E., Plescia J., Miles L. A. The plasminogen system and cell surfaces: evidence for plasminogen and urokinase receptors on the same cell type. J Cell Biol. 1986 Dec;103(6 Pt 1):2411–2420. doi: 10.1083/jcb.103.6.2411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Pyke C., Kristensen P., Ralfkiaer E., Grøndahl-Hansen J., Eriksen J., Blasi F., Danø K. Urokinase-type plasminogen activator is expressed in stromal cells and its receptor in cancer cells at invasive foci in human colon adenocarcinomas. Am J Pathol. 1991 May;138(5):1059–1067. [PMC free article] [PubMed] [Google Scholar]
  42. Pöllänen J., Hedman K., Nielsen L. S., Danø K., Vaheri A. Ultrastructural localization of plasma membrane-associated urokinase-type plasminogen activator at focal contacts. J Cell Biol. 1988 Jan;106(1):87–95. doi: 10.1083/jcb.106.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Reiser H., Coligan J., Palmer E., Benacerraf B., Rock K. L. Cloning and expression of a cDNA for the T-cell-activating protein TAP. Proc Natl Acad Sci U S A. 1988 Apr;85(7):2255–2259. doi: 10.1073/pnas.85.7.2255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Roldan A. L., Cubellis M. V., Masucci M. T., Behrendt N., Lund L. R., Danø K., Appella E., Blasi F. Cloning and expression of the receptor for human urokinase plasminogen activator, a central molecule in cell surface, plasmin dependent proteolysis. EMBO J. 1990 Feb;9(2):467–474. doi: 10.1002/j.1460-2075.1990.tb08132.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Saksela O., Rifkin D. B. Cell-associated plasminogen activation: regulation and physiological functions. Annu Rev Cell Biol. 1988;4:93–126. doi: 10.1146/annurev.cb.04.110188.000521. [DOI] [PubMed] [Google Scholar]
  46. Sappino A. P., Huarte J., Belin D., Vassalli J. D. Plasminogen activators in tissue remodeling and invasion: mRNA localization in mouse ovaries and implanting embryos. J Cell Biol. 1989 Nov;109(5):2471–2479. doi: 10.1083/jcb.109.5.2471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Schleef R. R., Loskutoff D. J. Fibrinolytic system of vascular endothelial cells. Role of plasminogen activator inhibitors. Haemostasis. 1988;18(4-6):328–341. doi: 10.1159/000215815. [DOI] [PubMed] [Google Scholar]
  48. Seifert S. C., Gelehrter T. D. Mechanism of dexamethasone inhibition of plasminogen activator in rat hepatoma cells. Proc Natl Acad Sci U S A. 1978 Dec;75(12):6130–6133. doi: 10.1073/pnas.75.12.6130. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Shih Y. J., Baynes R. D., Hudson B. G., Flowers C. H., Skikne B. S., Cook J. D. Serum transferrin receptor is a truncated form of tissue receptor. J Biol Chem. 1990 Nov 5;265(31):19077–19081. [PubMed] [Google Scholar]
  50. Skriver L., Nielsen L. S., Stephens R., Danø K. Plasminogen activator released as inactive proenzyme from murine cells transformed by sarcoma virus. Eur J Biochem. 1982 May 17;124(2):409–414. doi: 10.1111/j.1432-1033.1982.tb06608.x. [DOI] [PubMed] [Google Scholar]
  51. Stephens R. W., Pöllänen J., Tapiovaara H., Leung K. C., Sim P. S., Salonen E. M., Rønne E., Behrendt N., Danø K., Vaheri A. Activation of pro-urokinase and plasminogen on human sarcoma cells: a proteolytic system with surface-bound reactants. J Cell Biol. 1989 May;108(5):1987–1995. doi: 10.1083/jcb.108.5.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Stoppelli M. P., Corti A., Soffientini A., Cassani G., Blasi F., Assoian R. K. Differentiation-enhanced binding of the amino-terminal fragment of human urokinase plasminogen activator to a specific receptor on U937 monocytes. Proc Natl Acad Sci U S A. 1985 Aug;82(15):4939–4943. doi: 10.1073/pnas.82.15.4939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Strickland S., Reich E., Sherman M. I. Plasminogen activator in early embryogenesis: enzyme production by trophoblast and parietal endoderm. Cell. 1976 Oct;9(2):231–240. doi: 10.1016/0092-8674(76)90114-8. [DOI] [PubMed] [Google Scholar]
  54. Vassalli J. D., Baccino D., Belin D. A cellular binding site for the Mr 55,000 form of the human plasminogen activator, urokinase. J Cell Biol. 1985 Jan;100(1):86–92. doi: 10.1083/jcb.100.1.86. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Vihko K. K., Kristensen P., Danø K., Parvinen M. Immunohistochemical localization of urokinase-type plasminogen activator in Sertoli cells and tissue-type plasminogen activator in spermatogenic cells in the rat seminiferous epithelium. Dev Biol. 1988 Mar;126(1):150–155. doi: 10.1016/0012-1606(88)90248-5. [DOI] [PubMed] [Google Scholar]
  56. Williams A. F., Tse A. G., Gagnon J. Squid glycoproteins with structural similarities to Thy-1 and Ly-6 antigens. Immunogenetics. 1988;27(4):265–272. doi: 10.1007/BF00376121. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Cell Biology are provided here courtesy of The Rockefeller University Press

RESOURCES