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Abstract

Angiogenesis is thought to depend on a precise balance of positive and negative regulation. Angiopoietin-1 (Ang1) is an angiogenic factor that signals through the endothelial cell–specific Tie2 receptor tyrosine kinase. Like vascular endothelial growth factor, Ang1 is essential for normal vascular development in the mouse. An Ang1 relative, termed angiopoietin-2 (Ang2), was identified by homology screening and shown to be a naturally occurring antagonist for Ang1 and Tie2. Transgenic overexpression of Ang2 disrupts blood vessel formation in the mouse embryo. In adult mice and humans, Ang2 is expressed only at sites of vascular remodeling. Natural antagonists for vertebrate receptor tyrosine kinases are atypical; thus, the discovery of a negative regulator acting on Tie2 emphasizes the need for exquisite regulation of this angiogenic receptor system.

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Science
Volume 277 | Issue 5322
4 July 1997

Submission history

Received: 7 March 1997
Accepted: 13 May 1997
Published in print: 4 July 1997

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Authors

Affiliations

Peter C. Maisonpierre*
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Chitra Suri*
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Pamela F. Jones*,
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Sona Bartunkova*
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Stanley J. Wiegand
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Czeslaw Radziejewski
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Debra Compton
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Joyce McClain
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Thomas H. Aldrich
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Nick Papadopoulos
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Thomas J. Daly
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Samuel Davis*
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
Thomas N. Sato*
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.
George D. Yancopoulos*,
P. C. Maisonpierre, C. Suri, P. F. Jones, S. J. Wiegand, C. Radziejewski, D. Compton, J. McClain, T. H. Aldrich, N. Papadopoulos, T. J. Daly, S. Davis, and G. D. Yancopoulos are at Regeneron Pharmaceuticals Inc., 777 Old Saw Mill River Road, Tarrytown, NY 10591, USA. S. Bartunkova and T. N. Sato are at Beth Israel–Deaconess Medical Center and Harvard Medical School, 330 Brookline Avenue, Boston, MA 02215, USA.

Notes

*
These authors contributed equally to this article.
Present address: Molecular Medicine, St. James University Hospital, Leeds LS9 7TS, UK.
To whom correspondence should be addressed. E-mail: [email protected]

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