Skip to main content
SpringerLink
Log in

Interaction between kringle and growth-factor-like domains in the urokinase molecule: Possible role in stimulation of chemotaxis

  • Published:
Biochemistry (Moscow) Aims and scope Submit manuscript

Abstract

The results presented in this paper suggest the presence of an interaction between the kringle-and the growth-factor-like urokinase domains. This interaction regulates chemotactic properties of urokinase. We also show that interaction of urokinase with its “classical” receptor (uPAR) has a “permissive” effect on the interactions between the kringle domain and other targets on the cell surface. On the basis of our data we can suggest that uPAR serves as an “adaptor” for urokinase, and the binding of urokinase kringle domain to its receptor causes immediate activation of intracellular signaling and induction of cell migration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

ATF:

N-terminal fragment of urokinase

BSA:

bovine serum albumin

CHO:

Chinese hamster ovary

GFD:

growth-factor-like domain

GPI:

glycosyl phosphatidylinositol

HEK 293:

transformed human embryonic kidney cell line

HGF:

hepatocyte growth factor

KBP:

kringle-binding protein

KD:

kringle domain

LRP:

low density lipoprotein receptor related protein

PBS:

phosphate-buffered saline

PD:

proteolytic domain

PVDF:

polyvinylidene fluoride

RAP:

receptor-associated protein

SMC:

smooth muscle cells

uPA (urokinase):

urokinase-type plasminogen activator

uPA-GFD:

urokinase without growth-factor-like domain

uPAmut:

modified urokinase

uPAwt:

wild type urokinase

uPAR:

urokinase receptor

U937:

human leukemic monocyte lymphoma cell line

References

  1. Binder, B. R., Mihaly, J., and Prager, G. W. (2007) Thromb. Haemost., 97, 336–342.

    PubMed  CAS  Google Scholar 

  2. Crippa, M. P. (2007) Int. J. Biochem. Cell Biol., 39, 690–694.

    Article  PubMed  CAS  Google Scholar 

  3. Mukhina, S., Stepanova, V., Traktouev, D., Poliakov, A., Beabealashvilly, R., Gursky, Y., Minashkin, M., Shevelev, A., and Tkachuk, V. (2000) J. Biol. Chem., 275, 16450–16458.

    Article  PubMed  CAS  Google Scholar 

  4. Bdeir, K., Kuo, A., Sachais, B. S., Rux, A. H., Bdeir, Y., Mazar, A., Higazi, A. A., and Cines, D. B. (2003) Blood, 102, 3600–3608.

    Article  PubMed  CAS  Google Scholar 

  5. Behrendt, N., Ploug, M., Patthy, L., Houen, G., Blasi, F., and Dano, K. (1991) J. Biol. Chem., 266, 7842–7847.

    PubMed  CAS  Google Scholar 

  6. Behrendt, N., Ronne, E., and Dano, K. (1996) J. Biol. Chem., 271, 22885–22894.

    Article  PubMed  CAS  Google Scholar 

  7. Higazi, A. A., Mazar, A., Wang, J., Quan, N., Griffin, R., Reilly, R., Henkin, J., and Cines, D. B. (1997) J. Biol. Chem., 272, 5348–5353.

    Article  PubMed  CAS  Google Scholar 

  8. Barinka, C., Parry, G., Callahan, J., Shaw, D. E., Kuo, A., Bdeir, K., Cines, D. B., Mazar, A., and Lubkowski, J. (2006) J. Mol. Biol., 363, 482–495.

    Article  PubMed  CAS  Google Scholar 

  9. Ploug, M., Behrendt, N., Lober, D., and DaNo, K. (1991) Semin. Thromb. Hemost., 17, 183–193.

    Article  PubMed  CAS  Google Scholar 

  10. Busso, N., Masur, S. K., Lazega, D., Waxman, S., and Ossowski, L. (1994) J. Cell Biol., 126, 259–270.

    Article  PubMed  CAS  Google Scholar 

  11. Anichini, E., Fibbi, G., Pucci, M., Caldini, R., Chevanne, M., and del Rosso, M. (1994) Exp. Cell Res., 213, 438–448.

    Article  PubMed  CAS  Google Scholar 

  12. Dumler, I., Weis, A., Mayboroda, O. A., Maasch, C., Jerke, U., Haller, H., and Gulba, D. C. (1998) J. Biol. Chem., 273, 315–321.

    Article  PubMed  CAS  Google Scholar 

  13. Nguyen, D. H., Hussaini, I. M., and Gonias, S. L. (1998) J. Biol. Chem., 273, 8502–8507.

    Article  PubMed  CAS  Google Scholar 

  14. Waltz, D. A., Sailor, L. Z., and Chapman, H. A. (1993) J. Clin. Invest., 91, 1541–1552.

    Article  PubMed  CAS  Google Scholar 

  15. Chang, A. W., Kuo, A., Barnathan, E. S., and Okada, S. S. (1998) Thromb. Vasc. Biol., 18, 1855–1860.

    CAS  Google Scholar 

  16. Rabbani, S. A., Mazar, A. P., Bernier, S. M., Haq, M., Bolivar, I., Henkin, J., and Goltzman, D. (1992) J. Biol. Chem., 267, 14151–14156.

    PubMed  CAS  Google Scholar 

  17. Fishman, D. A., Kearns, A., Larsh, S., Enghild, J. J., and Stack, M. S. (1999) Biochemistry, 341, 765–769.

    Article  CAS  Google Scholar 

  18. Ossowski, L., and Aguirre-Ghiso, J. A. (2000) Curr. Opin. Cell Biol., 12, 613–620.

    Article  PubMed  CAS  Google Scholar 

  19. Monier, S., Parton, R. G., Vogel, F., Behlke, J., Henske, A., and Kurzchalia, T. V. (1995) Mol. Biol. Cell, 6, 911–927.

    PubMed  CAS  Google Scholar 

  20. Kjoller, L., and Hall, A. (2001) J. Cell Biol., 152, 1145–1157.

    Article  PubMed  CAS  Google Scholar 

  21. Gardsvoll, H., and Ploug, M. (2007) J. Biol. Chem., 282, 13561–13572.

    Article  PubMed  CAS  Google Scholar 

  22. Sitrin, R. G., Pan, P. M., Blackwood, R. A., Huang, J., and Petty, H. R. (2001) J. Immunol., 166, 4822–4825.

    PubMed  CAS  Google Scholar 

  23. Pluskota, E., Soloviev, D. A., and Plow, E. P. (2003) Blood, 101, 1582–1590.

    Article  PubMed  CAS  Google Scholar 

  24. Stepanova, V., Bobik, R., Bibilashvily, A., Belogurov, I., Rybalkin, S., Domogatsky, P., Little, J., Goncharova, E., and Tkachuk, V. (1997) FEBS Lett., 414, 471–474.

    Article  PubMed  CAS  Google Scholar 

  25. Asryants, R. A., Duszenkova, I. V., and Nagradova, N. K. (1985) Analyt. Biochem., 151, 571–574.

    Article  PubMed  CAS  Google Scholar 

  26. Towbin, H., Staehelin, T., and Gordon, G. (1979) Proc. Natl. Acad. Sci. USA, 76, 4350–4354.

    Article  PubMed  CAS  Google Scholar 

  27. Hansen, A. P., Petros, A. M., Meadows, R. P., Nettesheim, D. G., Mazar, A. P., Olejniczak, E. T., Xu, R. X., Pederson, T. M., Henkin, J., and Fesik, S. W. (1994) Biochemistry, 33, 4847–4864.

    Article  PubMed  CAS  Google Scholar 

  28. Bogusky, M. J., Dobson, C. M., and Smith, R. A. (1989) Biochemistry, 28, 6728–6735.

    Article  PubMed  CAS  Google Scholar 

  29. Nagradova, N. K. (2002) Biochemistry (Moscow), 67, 839–849.

    Article  CAS  Google Scholar 

  30. Chirgadze, D. Y., Hepple, J. P., Zhou, H., Byrd, R. A., Blundell, T. L., and Gherardi, E. (1999) Nat. Struct. Biol., 6, 72–79.

    Article  PubMed  CAS  Google Scholar 

  31. Pluskota, E., Soloviev, D. A., Bdeir, K., Cines, D. B., and Plow, E. F. (2004) J. Biol. Chem., 279, 18063–18072.

    Article  PubMed  CAS  Google Scholar 

  32. Kwak, S. H., Mitra, S., Bdeir, K., Strassheim, D., Park, J. S., Kim, J. Y., Idell, S., Cines, D., and Abraham, E. (2005) J. Leukoc. Biol., 78, 937–945.

    Article  PubMed  CAS  Google Scholar 

  33. Poliakov, A. A., Mukhina, S. A., Traktouev, D. O., Bibilashvily, R. S., Gursky, Y. G., Minashkin, M. M., Stepanova, V. V., and Tkachuk, V. A. (1999) J. Recept. Signal Transduct. Res., 19, 939–951.

    Article  PubMed  CAS  Google Scholar 

  34. Goncharova, E. A., Vorotnikov, A. V., Gracheva, E. O., Wang, C. L., Panettieri, R. A., Jr., Stepanova, V. V., and Tkachuk, V. A. (2002) Biol. Chem., 383, 115–126.

    Article  PubMed  CAS  Google Scholar 

  35. Nykjaer, A., Kjoller, L., Cohen, R. L., Lawrence, D. A., Garni-Wagner, B. A., Todd, R. F., van Zonneveld, A. J., Gliemann, J., and Andreasen, P. A. (1994) J. Biol. Chem., 269, 25668–25676.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Russian Cardiology Research Center, Ministry of Health of Russian Federation, 3-ya Cherepkovskaya ul. 15a, 121552, Moscow, Russia

    V. V. Stepanova, I. B. Beloglazova, Y. G. Gursky, R. S. Bibilashvily, Y. V. Parfyonova & V. A. Tkachuk

  2. Faculty of Fundamental Medicine, Lomonosov Moscow State University, Lomonosovsky pr. 31/5, 119192, Moscow, Russia

    V. A. Tkachuk

Authors
  1. V. V. Stepanova
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. I. B. Beloglazova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Y. G. Gursky
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. S. Bibilashvily
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y. V. Parfyonova
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. V. A. Tkachuk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. V. Parfyonova.

Additional information

Original Russian Text © V. V. Stepanova, I. B. Beloglazova, Y. G. Gursky, R. S. Bibilashvily, Y. V. Parfyonova, V. A. Tkachuk, 2008, published in Biokhimiya, 2008, Vol. 73, No. 3, pp. 311–321.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM07-243, February 10, 2008.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stepanova, V.V., Beloglazova, I.B., Gursky, Y.G. et al. Interaction between kringle and growth-factor-like domains in the urokinase molecule: Possible role in stimulation of chemotaxis. Biochemistry Moscow 73, 252–260 (2008). https://doi.org/10.1134/S0006297908030036

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0006297908030036

Key words

Search

Navigation