Abstract
Fibrinogen, fibrin, and related fragments have varying stimulatory effects on the initial rate of the activation of human plasminogen ([Glu1]Pg) by recombinant tissue plasminogen activator (rt-PA). A detailed analysis of this enhancement was undertaken using various purified and complexed forms of the known domains of fibrin(ogen) with a view to gaining additional knowledge regarding the substructures of fibrinogen and fibrin that are important for their stimulatory capacities. Both arvin-mediated fibrin, as well as fibrinogen fragments generated as a result of its cleavage with CNBr, stimulate the activation in a biphasic manner, most likely as a result of changes in the promoter molecule accompanying the denaturation processes that are normally employed to either solubilize or generate these particular promoters. Using purified fibrinogen and fibrin fragments, it was found that fragment E, which binds to [Glu1]Pg, does not enhance the activation reaction, while fragment D1 has a potentiating effect. This suggests that the binding of [Glu1]Pg to fibrin(ogen) alone is not, in itself, sufficient for stimulation of activation to occur, but that the rt-PA-fibrin(ogen) interaction is fundamental to this same process. All purified and mixtures of fragments containing the fragment D domain (e.g., D2E, X-oligomer, fragment X) stimulate the reaction to a greater degree than fibrinogen and fragment D1. It is concluded that the fibrinogen D domain is asine qua non for the enhancement reaction, while structures containing the E domain had a symbiotic effect on enhancement.
Similar content being viewed by others
References
Astedt, B., Lecander, I., Brodin, T., Lundblad, A., and Low, K. (1985).Thromb. Haemost. 53, 122–125.
Brockway, W. J., and Castellino, F. J. (1972). Arch. Biochem. Biophys.151, 194–199.
Camiolo, S. M., Thorsen, S., and Astrup, Y. (1971).Proc. Soc. Exp. Biol. Med. 138, 277–280.
Chesterman, C. N., Allington, M. J., and Sharp, A. A. (1972).Nature (Lond.)238, 15–17.
Chibber, B. A. K., Radek, J. T., Morris, J. P., and Castellino, F. J. (1986).Proc. Natl. Acad. Sci. USA 83, 1237–1241.
Christensen, U. (1985).FEBS Lett. 182, 43–46.
Collen, D. (1976).Eur. J. Biochem. 69, 209–216.
Dunn, F. W., Deguchi, K., Soria, J., Soria, C., Lijnen, H. R., Tobelem, G., and Caen, J. (1984).Thromb. Res. 36, 345–351.
Francis, C. W., and Marder, V. J. (1982).Semin. Thromb. Haemost. 8, 57–68.
Gaffney, P. J., Joe, F., and Mahmoud, M. (1980).Thromb. Res. 20, 647–662.
Gaffney, P. J., and Joe, F. (1979).Thromb. Res. 15, 673–687.
Gaffney, P. J., Creighton, L. C., Pring, J. B., and Mahmoud, M. (1985).Thromb. Haemost. 54, 270 (abst.).
Graeff, H., and Hafter, R. (1982).Semin. Thromb. Haemost. 48, 266–269.
Harpel, P. C., Chang, T. S., and Verderker, E. (1985).J. Biol. Chem. 260, 4432–4440.
Hoylaerts, M., Rijken, D. C., Lijnen, H. R., and Collen, D. (1982).J. Biol. Chem. 257, 2912–2919.
Kimura, S., and Aoki, N. (1986).J. Biol. Chem. 261, 15591–15595.
Kruithof, E. K. O., Tran-Thang, C., Rawsijn, A., and Bachmann, F. (1984).Blood 64, 907–913.
Laudano, A. P., and Doolittle, R. F. (1979).Proc. Natl. Acad. Sci. USA 75, 3085–3089.
Lucas, M. A., Straight, D. L., Fretto, L. J., and McKee, P. A. (1983).J. Biol. Chem. 258, 12171–12177.
Mullertz, S., and Clemmensen, I. (1976).Biochem. J. 159, 545–553.
Norrman, B., Wallen, P., and Ranby, M. (1985).Eur. J. Biochem. 149, 193–200.
Nussenzweig, V., Selig, M., Pelmont, J., and Grabar, P. (1961).Ann. Inst. Pasteur 100, 377–387.
Ranby, M. (1982).Biochim. Biophys. Acta 704, 461–469.
Ranby, M., Norman, B., and Wallen, P. (1982).Thromb. Res. 27, 743–749.
Sherry, S., Fletcher, A. P., and Alkjaersig, N. (1959).Physiol. Rev. 39, 343–382.
Suenson, E., and Petersen, L. C. (1986).Biochim. Biophys. Acta 870, 510–519.
Suenson, E., Lutzen, O., and Thorsen, S. (1984).Eur. J. Biochem. 140, 513–522.
Takada, Y., Makino, Y., and Takada, A. (1985).Thromb. Res. 39, 289–296.
Thorsen, S. (1975).Biochim. Biophys. Acta 393, 55–65.
TIMI Study Group (1985).N. Engl. J. Med. 312, 932–936.
Tran-Thang, C., Kruithof, E. K. O., and Bachmann, F. (1984).J. Clin. Invest. 74, 2009–2016.
Tran-Thang, C., Kruithof, E. K. O., Atkinson, J., and Bachmann, F. (1986).Eur. J. Biochem. 160, 4432–4440.
Urano, T., deSerrano, V.S., Chibber, B. A. K., and Castellino, F. J. (1987).J. Biol. Chem. 262, 15959–15964.
Urano, T., deSerrano, V. S., Gaffney, P. J., and Castellino, F. J. (1988a).Biochemistry 27, 6522–6528.
Urano, T., Urano, S., and Castellino, F. J. (1988b).Biochem. Biophys. Res. Commun. 150, 45–51.
van Mourik, J. A., Lawrence, D. A., and Loskutoff, D. J. (1984).J. Biol. Chem. 259, 14914–14921.
Varadi, A., and Patthy, L. (1983).Biochemistry 22, 2440–2446.
Varadi, A., and Patthy, L. (1984).Biochemistry 23, 2108–2112.
Verheijen, J. H., Mullaart, E., Chang, G. T. G., Kluft, C., and Vijngaards, G. (1982).Thromb. Haemorrh. 48, 266–269.
Verheijen, J. H., Chang, G. T. G., and Kluft, C. (1984).Thromb. Haemost. 51, 392–395.
Violand, B. N., and Castellino, F. J. (1976).J. Biol. Chem. 251, 3906–3912.
Whitaker, A. N., Rowe, E. A., Masci, P. P., Joe, F., and Gaffney, P. J. (1980).Thromb. Res. 19, 381–391.
Wiman, B., and Collen, D. (1978).Nature (Lond.)272, 549–550.
Wiman, B., Chimielewska, J., and Ranby, M. (1984).J. Biol. Chem. 259, 3644–3647.
Wun, T.-C., Ossowski, L., and Reich, E. (1982).J. Biol. Chem. 257, 7262–7268.
Author information
Authors and Affiliations
Additional information
On study leave from the National Institute for Biological Standards and Control, South Mimms, HERTS EN6 3QG, England.
Rights and permissions
About this article
Cite this article
de Serrano, V.S., Urano, T., Gaffney, P.J. et al. Influence of various structural domains of fibrinogen and fibrin on the potentiation of plasminogen activation by recombinant tissue plasminogen activator. J Protein Chem 8, 61–77 (1989). https://doi.org/10.1007/BF01025079
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/BF01025079