Abstract
Human neutrophil elastase cleaves angiogenin at the Ile-29/Met-30 peptide bond to produce two major disulfide-linked fragments with apparent molecular weights of 10,000 and 4000, respectively. Elastase-cleaved angiogenin has slightly increased ribonucleolytic activity, but has lost its ability to undergo nuclear translocation in endothelial cells, a process essential for angiogenic activity. Cleavage appears to alter the cell-binding properties of angiogenin, despite the fact that it occurs some distance from the putative receptor-binding site, since the elastase-cleaved protein fails to compete with its native counterpart for nuclear translocation in endothelial cells. Plasminogen specifically accelerates elastase proteolysis of angiogenin. It does not enhance elastase activity toward ribonuclease A or the synthetic peptide substrate MeOSuc-Ala-Ala-Pro-Val-pNA. Plasminogen-accelerated inactivation of angiogenin by elastase might be a significant event in the process of angiogenin-induced angiogenesis since (i) angiogenin and plasminogen circulate in plasma at high concentrations, (ii) angiogenin, especially when bound to actin, activates tissue plasminogen activator to generate plasmin from plasminogen, and (iii) elastase cleaves plasminogen to produce angiostatin, a potent inhibitor of angiogenesis and metastasis. Interrelationships among angiogenin, plasminogen, plasminogen activators, elastase, and angiostatin may provide a sensitive regulatory system to balance angiogenesis and antiangiogenesis.
Similar content being viewed by others
REFERENCES
Acharya, K. R., Shapiro, R., Allen, S. C., Riordan, J. F., and Vallee, B. L. (1994). Proc. Natl. Acad. Sci. USA 91, 2915–2919.
Badet, J., Soncin, F., Guitton, J. D., Lamare, O., Cartwright, T., and Barritault, D. (1989). Proc. Natl. Acad. Sci. USA 86, 8427–8431.
Baugh, R. J., and Travis, J. (1976). Biochemistry 15, 836–841.
Bicknell, R., and Vallee, B. L. (1988). Proc. Natl. Acad. Sci. USA 85, 5961–5965.
Bicknell, R., and Vallee, B. L. (1989). Proc. Natl. Acad. Sci. USA 86, 1573–1577.
Bläser, J., Triebl, S., Kopp, C., and Tschesche, H. (1993). Eur. J. Clin. Chem. Clin. Biochem. 31, 513–516.
Del Mar, E. G., Largman, C., Brodrick, J. W., Fassett, M., and Geokas, M. C. (1980). Biochemistry 19, 468–472.
Fett, J. W., Strydom, D. J., Lobb, R. R., Alderman, E. M., Bethune, J. L., Riordan, J. F., and Vallee, B. L. (1985). Biochemistry 24, 5480–5486.
Fett, J. W., Olson, K. A., and Rybak, S. M. (1994). Biochemistry 33, 5421–5427.
Folkman, J., and Klagsbrun, M. (1987). Science 235, 442–447.
Folkman, J., and Shing, Y. (1992). J. Biol. Chem. 267, 10931–10934.
Hallahan, T. W., Shapiro, R., and Vallee, B. L. (1991). Proc. Natl. Acad. Sci. USA 88, 2222–2226.
Harper, J. W., and Vallee, B. L. (1988). J. Protein Chem. 7, 355–363.
Hu, G.-F. (1995). J. Chromatogr. 705, 89–103.
Hu, G.-F., and Riordan, J. F. (1993). Biochem. Biophys. Res. Commun. 197, 682–687.
Hu, G.-F., Strydom, D. J., Fett, J. W., Riordan, J. F., and Vallee, B. L. (1993). Proc. Natl. Acad. Sci. USA 90, 1217–1221.
Hu, G.-F., Riordan, J. F., and Vallee, B. L. (1994). Proc. Natl. Acad. Sci. USA 91, 12096–12100.
Hu, G.-F., Riordan, J. F., and Vallee, B. L. (1997). Proc. Natl. Acad. Sci. USA 94, 2204–2209.
Jim, S-I., Ito, K-I., Kohno, K., Ono, M., Kuwano, M., Itagaki, Y., and Isikawa, H. (1995). Biochem. Biophys. Res. Commun. 211, 476–483.
King, T. V., and Vallee, B. L. (1991). J. Bone Joint Surg. 73-B, 587–590.
Klagsbrun, M., and D'Amore, P. A. (1991). Annu. Rev. Physiol. 53, 217–239.
Klee, W. A. (1965). J. Biol. Chem. 240, 2900–2906.
Kolev, K., Léránt, I., Tenekejiev, K., and Machovich, R. (1994). J. Biol. Chem. 269, 17030–17034.
Kurachi, K., Davie, E. W., Strydom, D. J., Riordan, J. F., and Vallee, B. L. (1985). Biochemistry 24, 5494–5499.
Laursen, R. A., Dixon, J. D., Liang, S. P., Nguyen, D. M., Kelcourse, T., Udell, L., and Pappin, D. J. C. (1989). In Methods in Protein Sequence Analysis (Wittman-Leibold, B., ed.), Springer-Verlag, Berlin, pp. 61–68.
Machovich, R., and Owen, W. G. (1989). Biochemistry 28, 4517–4522.
Matheson, N. R., Wong, P. S., Schuyler, M., and Travis, J. (1981). Biochemistry 20, 331–336.
Moroinau, J., and Riordan, J. F. (1994a). Proc. Natl. Acad. Sci. USA 91, 1677–1681.
Moroianu, J., and Riordan, J. F. (1994b). Biochem. Biophys. Res. Commun. 203, 1765–1772.
Navia, M. A., McKeever, B. M., Springer, J. P., Lin, T. Y., Williams, H. R., Fluder, E. M., Dorn, C. P., and Hoogsteen, K. (1989). Proc. Natl. Acad. Sci. USA 86, 7–11.
Niewiarowski, S., Regoeczi, E., and Mustard, J. F. (1972). Ann. N. Y. Acad. Sci. 201, 72–83.
O'Reilly, M. S., Holmgren, L., Shing, Y., Chen, C., Rosenthal, R. A., Moses, M., Lane, W. S., Cao, Y., Sage, E. H., and Folkman, J. (1994). Cell 79, 315–328.
Perona, J. J., and Craik, C. S. (1995). Protein Sci. 4, 337–360.
Schott, R. J., and Marrow, L. A. (1993). Cardiovasc. Res. 27, 1155–1161.
Shapiro, R., and Vallee, B. L. (1987). Proc. Natl. Acad. Sci. USA 84, 2238–2241.
Shapiro, R., Weremowicz, S., Riordan, J. F., and Vallee, B. L. (1987). Proc. Natl. Acad. Sci. USA 84, 8783–8787.
Shapiro, R., Harper, J. W., Fox, E. A., Jansen, H.-W., Hein, F., and Uhlmann, E. (1988). Anal. Biochem. 175, 450–461.
Shapiro, R., Riordan, J. F., and Vallee, B. L. (1989). Biochemistry 28, 1726–1732.
Shimoyama, S., Gansauge, F., Gansauge, S., Negri, G., Oohara, T., and Beger, H. G. (1996). Cancer Res. 56, 2703–2706.
Soncin, F. (1992). Proc. Natl. Acad. Sci. USA 89, 2232–2236.
Stein, R. L., Strimpler, A. M., Hori, H., and Powers, J. C. (1987). Biochemistry 26, 1301–1305.
Strydom, D. J., Fett, J. W., Lobb, R. R., Alderman, E. M., Bethune, J. R., Riordan, J. F., and Vallee, B. L. (1985). Biochemistry 24, 5486–5494.
Travis, J., and Salvesen, G. S. (1983). Annu. Rev. Biochem. 52, 655–709.
Tschesche, H., Kopp, C., Hörl, W. H., and Hempelmann, U. (1994). J. Biol. Chem. 269, 30274–30280.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Hu, Gf. Limited Proteolysis of Angiogenin by Elastase Is Regulated by Plasminogen. J Protein Chem 16, 669–679 (1997). https://doi.org/10.1023/A:1026302419881
Published:
Issue Date:
DOI: https://doi.org/10.1023/A:1026302419881