Angiopoietin-2, a Natural Antagonist for Tie2 That Disrupts in vivo Angiogenesis

American Association for the Advancement of Science (AAAS) - Tập 277 Số 5322 - Trang 55-60 - 1997
Peter C. Maisonpierre1, Chitra Suri1, Pamela F. Jones1, Sona Bartunkova1, Stanley J. Wiegand1, Czeslaw Radziejewski1, Debra Compton1, Joyce McClain1, Thomas H. Aldrich1, Nikolaos G. Papadopoulos1, Thomas J. Daly1, Samuel Davis1, Thomas T. Sato1, George D. Yancopoulos1
1P. 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.

Tóm tắt

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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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.

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American Association for the Advancement of Science (AAAS)

Tập 277 Số 5322

55-60

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