Angiopoietins 3 and 4: Diverging gene counterparts in mice and humans

David M. Valenzuela, Jennifer A. Griffiths, Jose Rojas, Thomas H. Aldrich, Pamela F. Jones, Hao Zhou, Joyce Mcclain, Neal G. Copeland, Debra J. Gilbert, Nancy A. Jenkins, Tammy Huang, Nick Papadopoulos, Peter C. Maisonpierre, Samuel Davis, George D. Yancopoulos

Research output: Contribution to journalArticlepeer-review

402 Scopus citations


The angiopoietins have recently joined the members of the vascular endothelial growth factor family as the only known growth factors largely specific for vascular endothelium. The angiopoietins include a naturally occurring agonist, angiopoietin-1, as well as a naturally occurring antagonist, angiopoietin-2, both of which act by means of the Tie2 receptor. We now report our attempts to use homology-based cloning approaches to identify new members of the angiopoietin family. These efforts have led to the identification of two new angiopoietins, angiopoietin-3 in mouse and angiopoietin-4 in human; we have also identified several more distantly related sequences that do not seem to be true angiopoietins, in that they do not bind to the Tie receptors. Although angiopoietin-3 and angiopoietin-4 are strikingly more structurally diverged from each other than are the mouse and human versions of angiopoietin-1 and angiopoietin-2, they appear to represent the mouse and human counterparts of the same gene locus, as revealed in our chromosomal localization studies of all of the angiopoietins in mouse and human. The structural divergence of angiopoietin-3 and angiopoietin-4 appears to underlie diverging functions of these counterparts. Angiopoietin-3 and angiopoietin-4 have very different distributions in their respective species, and angiopoietin-3 appears to act as an antagonist, whereas angiopoietin-4 appears to function as an agonist.

Original languageEnglish (US)
Pages (from-to)1904-1909
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number5
StatePublished - Mar 2 1999


  • Angiogenesis
  • Tie receptor tyrosine kinase
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Genetics
  • General


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