Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis

Science

Volumn 277, Issue 5322, 1997, Pages 55-60

  Maisonpierre, Peter C ^a   Suri, Chitra ^a   Jones, Pamela F ^a,c   Bartunkova, Sona ^b   Wiegand, Stanley J ^a   Radziejewski, Czeslaw ^a   Compton, Debra ^a   McClain, Joyce ^a   Aldrich, Thomas H ^a   Papadopoulos, Nick ^a   Daly, Thomas J ^a   Davis, Samuel ^a   Sato, Thomas N ^b   Yancopoulos, George D ^a  

^a REGENERON PHARMACEUTICALS INC   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

^c ST JAMES S UNIVERSITY HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ANGIOGENIC FACTOR; ANGIOPOIETIN 1; ANGIOPOIETIN 2; PROTEIN TYROSINE KINASE; UNCLASSIFIED DRUG; VASCULOTROPIN;

ANGIOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; EMBRYO; ENDOTHELIUM CELL; GENE EXPRESSION; HUMAN; HUMAN CELL; HUMAN TISSUE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RECEPTOR BINDING; TRANSGENIC MOUSE;

AMINO ACID SEQUENCE; ANGIOPOIETIN-1; ANGIOPOIETIN-2; ANIMALS; BLOOD VESSELS; CELLS, CULTURED; CLONING, MOLECULAR; EMBRYO; ENDOTHELIAL GROWTH FACTORS; ENDOTHELIUM, VASCULAR; FEMALE; HUMANS; LIGANDS; LYMPHOKINES; MEMBRANE GLYCOPROTEINS; MICE; MICE, TRANSGENIC; MOLECULAR SEQUENCE DATA; NEOVASCULARIZATION, PHYSIOLOGIC; PHOSPHORYLATION; PROTEINS; RATS; RATS, SPRAGUE-DAWLEY; RECEPTOR PROTEIN-TYROSINE KINASES; RECEPTOR, TIE-2; RECOMBINANT FUSION PROTEINS; SIGNAL TRANSDUCTION; VASCULAR ENDOTHELIAL GROWTH FACTOR A; VASCULAR ENDOTHELIAL GROWTH FACTORS;

EID: 15144358851     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.277.5322.55     Document Type: Article

References (42)

1. W. Risau, FASEB J. 9, 926 (1995); Nature 386, 671 (1997).
2. W. Risau, FASEB J. 9, 926 (1995); Nature 386, 671 (1997).
3. J. Folkman, Nature Med. 1, 27 (1995).
4. D. Hanahan and J. Folkman, Cell 86, 353 (1996).
5. T. Mustonen and K. Alitalo, J. Cell Biol. 129, 895 (1995).
6. G. H. Fong, J. Rossant, M. Gertenstein, M. L. Breitman, Nature 376, 66 (1995); F. Shalaby et al., ibid., p. 62; P. Carmeliet et al., ibid. 380, 435 (1996); N. Ferrara et al., ibid., p. 439.
7. G. H. Fong, J. Rossant, M. Gertenstein, M. L. Breitman, Nature 376, 66 (1995); F. Shalaby et al., ibid., p. 62; P. Carmeliet et al., ibid. 380, 435 (1996); N. Ferrara et al., ibid., p. 439.
8. G. H. Fong, J. Rossant, M. Gertenstein, M. L. Breitman, Nature 376, 66 (1995); F. Shalaby et al., ibid., p. 62; P. Carmeliet et al., ibid. 380, 435 (1996); N. Ferrara et al., ibid., p. 439.
9. G. H. Fong, J. Rossant, M. Gertenstein, M. L. Breitman, Nature 376, 66 (1995); F. Shalaby et al., ibid., p. 62; P. Carmeliet et al., ibid. 380, 435 (1996); N. Ferrara et al., ibid., p. 439.
10. D. Jackson, O. V. Volpert, N. Bouck, D. I. H. Linzer, Science 266, 1581 (1994).
11. M. S. O'Reilly et al., Cell 79, 315 (1994).
12. M. S. O'Reilly et al., ibid. 88, 277 (1997).
13. S. Davis et al., ibid. 87, 1161 (1996).
14. D. J. Dumont, T. P. Yamaguchi, R. A. Conlon, J. Rossant, M. L. Breitman, Oncogene 7, 1471 (1992); P. C. Maisonpierre, M. Goldfarb, G. D. Yancopoulos, G. Gao, ibid. 8, 1631 (1993); T. N. Sato, Y. Qin, C. A. Kozak, K. L. Audus, Proc. Natl. Acad. Sci. U.S.A. 90, 9355 (1993); H. Schnurch and W. Risau, Development 119, 957 (1993); S. F. Ziegler, T. A. Bird, K. A. Schneringer, K. A. Schooley, P. R. Baum, Oncogens 8, 663 (1993).
15. D. J. Dumont, T. P. Yamaguchi, R. A. Conlon, J. Rossant, M. L. Breitman, Oncogene 7, 1471 (1992); P. C. Maisonpierre, M. Goldfarb, G. D. Yancopoulos, G. Gao, ibid. 8, 1631 (1993); T. N. Sato, Y. Qin, C. A. Kozak, K. L. Audus, Proc. Natl. Acad. Sci. U.S.A. 90, 9355 (1993); H. Schnurch and W. Risau, Development 119, 957 (1993); S. F. Ziegler, T. A. Bird, K. A. Schneringer, K. A. Schooley, P. R. Baum, Oncogens 8, 663 (1993).
16. D. J. Dumont, T. P. Yamaguchi, R. A. Conlon, J. Rossant, M. L. Breitman, Oncogene 7, 1471 (1992); P. C. Maisonpierre, M. Goldfarb, G. D. Yancopoulos, G. Gao, ibid. 8, 1631 (1993); T. N. Sato, Y. Qin, C. A. Kozak, K. L. Audus, Proc. Natl. Acad. Sci. U.S.A. 90, 9355 (1993); H. Schnurch and W. Risau, Development 119, 957 (1993); S. F. Ziegler, T. A. Bird, K. A. Schneringer, K. A. Schooley, P. R. Baum, Oncogens 8, 663 (1993).
17. D. J. Dumont, T. P. Yamaguchi, R. A. Conlon, J. Rossant, M. L. Breitman, Oncogene 7, 1471 (1992); P. C. Maisonpierre, M. Goldfarb, G. D. Yancopoulos, G. Gao, ibid. 8, 1631 (1993); T. N. Sato, Y. Qin, C. A. Kozak, K. L. Audus, Proc. Natl. Acad. Sci. U.S.A. 90, 9355 (1993); H. Schnurch and W. Risau, Development 119, 957 (1993); S. F. Ziegler, T. A. Bird, K. A. Schneringer, K. A. Schooley, P. R. Baum, Oncogens 8, 663 (1993).
18. D. J. Dumont, T. P. Yamaguchi, R. A. Conlon, J. Rossant, M. L. Breitman, Oncogene 7, 1471 (1992); P. C. Maisonpierre, M. Goldfarb, G. D. Yancopoulos, G. Gao, ibid. 8, 1631 (1993); T. N. Sato, Y. Qin, C. A. Kozak, K. L. Audus, Proc. Natl. Acad. Sci. U.S.A. 90, 9355 (1993); H. Schnurch and W. Risau, Development 119, 957 (1993); S. F. Ziegler, T. A. Bird, K. A. Schneringer, K. A. Schooley, P. R. Baum, Oncogens 8, 663 (1993).
19. A. Iwama et al., Biochem. Biophys. Res. Commun. 195, 301 (1993).
20. D. J. Dumont et al., Genes Dev. 8, 1897 (1994); T. N. Sato et al., Nature 376, 70 (1995).
21. D. J. Dumont et al., Genes Dev. 8, 1897 (1994); T. N. Sato et al., Nature 376, 70 (1995).
22. C. Suri et al., Cell 87, 1171 (1996).
23. 32P-labeled Ang1 cDNA probe at 55° or 65°C (25).
24. 245 that is easier to produce and purify) was used instead of Ang1; for details on expression and purification of Ang1, Ang1*, and Ang2, see S. Davis et al., in preparation.
25. J. Partanen et al., Mol. Cell. Biol. 12, 1698 (1992).
26. P. C. Maisonpierre et al., data not shown.
27. K. K. Hirschi and P. A. D'Amore, Cardiovasc. Res. 32, 687 (1996).
28. J. K. Findlay, J. Endocrinol. 111, 357 (1986); H. S. Phillips, J. Hains, D. W. Leung, N. Ferrara, Endocrinology 127, 965 (1990); D. Shweiki, A. Itin, G. Neufeld, H. Gitay-Goren, E. Keshet, J. Clin. Invest. 91, 2235 (1993); E. Bacharach, A. Itin, E. Keshet, Proc. Natl. Acad. Sci. U.S.A. 89, 10686 (1992).
29. J. K. Findlay, J. Endocrinol. 111, 357 (1986); H. S. Phillips, J. Hains, D. W. Leung, N. Ferrara, Endocrinology 127, 965 (1990); D. Shweiki, A. Itin, G. Neufeld, H. Gitay-Goren, E. Keshet, J. Clin. Invest. 91, 2235 (1993); E. Bacharach, A. Itin, E. Keshet, Proc. Natl. Acad. Sci. U.S.A. 89, 10686 (1992).
30. J. K. Findlay, J. Endocrinol. 111, 357 (1986); H. S. Phillips, J. Hains, D. W. Leung, N. Ferrara, Endocrinology 127, 965 (1990); D. Shweiki, A. Itin, G. Neufeld, H. Gitay-Goren, E. Keshet, J. Clin. Invest. 91, 2235 (1993); E. Bacharach, A. Itin, E. Keshet, Proc. Natl. Acad. Sci. U.S.A. 89, 10686 (1992).
31. J. K. Findlay, J. Endocrinol. 111, 357 (1986); H. S. Phillips, J. Hains, D. W. Leung, N. Ferrara, Endocrinology 127, 965 (1990); D. Shweiki, A. Itin, G. Neufeld, H. Gitay-Goren, E. Keshet, J. Clin. Invest. 91, 2235 (1993); E. Bacharach, A. Itin, E. Keshet, Proc. Natl. Acad. Sci. U.S.A. 89, 10686 (1992).
32. T. M. Schlaeger et al., Proc. Natl. Acad. Sci. U.S.A. 94, 3058 (1997).
33. R. Schweitzer, R. Howes, R. Smith, B.-Z. Shilo, M. Freeman, Nature 376, 699 (1995).
34. V. Cioce et al., J. Biol. Chem. 271, 13110 (1996).
35. W. P. Arend, H. G. Welgus, R. C. Thompson, S. P. Eisenberg, J. Clin. Invest. 85, 1694 (1990).
36. M. Vikkula et al., Cell 87, 1181 (1996).
37. P. C. Maisonpierre et al., Science 247, 1446 (1990).
38. C.-J. S. Edgell, C. C. McDonald, J. B. Graham, Proc. Natl. Acad. Sci. U.S.A. 80, 3734 (1983).
39. P. C. Maisonpierre, P. F. Jones, S. Davis, G. D. Yancopoulos, in preparation.
40. Probes for mouse embryo sections were 560-and 680-nucteotide (nt) cRNAs extending from 5′ leader sequence to, respectively, codon 165 in mouse Ang1 cDNA and codon 155 in mouse Ang2 cDNA. Probes for rat ovary sections were VEGF, a 141-nt cRNA spanning the last 47 rat VEGF codons (which are shared among most VEGF RNA splice-variants); Ang1, a 773-nt cRNA spanning the last 257 codons of mouse Ang1 cDNA; and Ang2, a 315-nt cRNA spanning codons 380 to 485 in rat Ang2 cDNA.
41. To obtain staged ovulating ovarian tissue, we injected immature (postnatal day 29) female Sprague-Dawley rats (Zivic-Miller) with 5 U of pregnant mare serum gonadotropin (Calbiochem). Rats were killed and ovaries were surgically removed beginning at 56 hours after injection and at 9-to 32-hour intervals thereafter.
42. We thank L. S. Schleifer and P. R. Vagelos for enthusiastic support; M. Goldfarb, M. Wang, R. Rossman, D. Datta, Y. Qing, T. Schlaeger, J. Lawitts, and J. Bruno for their contributions; J. Springhorn for HUCEC cells; and C. Murphy, E. Hubel, C. Rudowsky, and E. Burrows for graphics work. T.N.S. was partly supported by Hoffmann-LaRoche Inc.