{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T11:06:03Z","timestamp":1791198363098,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2004,8,1]],"date-time":"2004-08-01T00:00:00Z","timestamp":1091318400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2004,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The angiopoietin (Ang) family of growth factors includes Ang1, Ang2, Ang3, and Ang4, all of which bind to the endothelial receptor tyrosine kinase Tie2. Ang3 (mouse) and Ang4 (human) are interspecies orthologs. In experiments with human endothelial cell lines, Ang3 was identified as an antagonist of Tie2 and Ang4 was identified as an agonist of Tie2. However, the biological roles of Ang3 and Ang4 are unknown. We examined the biological effect of recombinant Ang3 and Ang4 proteins in primary cultured endothelial cells and in vivo in mice. Recombinant Ang3 and Ang4 formed disulfide\u2010linked dimers. Ang4 (400 ng\/mL) markedly increased Tie2 and Akt phosphorylation in primary cultured HUVECs whereas Ang3 (400 ng\/mL) did not produce significant changes. Accordingly, Ang4, but not Ang3, induced survival and migration in primary cultured HUVECs. Unexpectedly, intravenously administered Ang3 (30 \u00b5g) was more potent than Ang4 (30 \u00b5g) in phosphorylating the Tie2 receptor in lung tissue from mice in vivo. Accordingly, Ang3 was more potent than Ang4 in phosphorylating Akt in primary cultured mouse lung microvascular endothelial cells. Ang3 and Ang4 both produced potent corneal angiogenesis extending from the limbus across the mouse cornea in vivo. Thus, Ang3 and Ang4 are agonists of Tie2, but mouse Ang3 has strong activity only on endothelial cells of its own species.\u2014Lee, H. J., Cho, C.\u2010H., Hwang, S.\u2010J., Choi, H.\u2010H., Kim, K.\u2010T., Ahn, S. Y., Kim, J.\u2010H., Oh, J.\u2010L., Lee, G. M., Koh, G. Y. Biological characterization of angiopoietin\u20103 and angiopoietin\u20104.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 18, 1200\u20131208 (2004)\n                  <\/jats:p>","DOI":"10.1096\/fj.03-1466com","type":"journal-article","created":{"date-parts":[[2004,7,30]],"date-time":"2004-07-30T02:33:02Z","timestamp":1091154782000},"page":"1200-1208","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":147,"title":["Biological characterization of angiopoietin\u20103 and angiopoietin\u20104"],"prefix":"10.1096","volume":"18","author":[{"given":"Hyuek Jong","family":"Lee","sequence":"first","affiliation":[{"name":"Biomedical Research Center and Department of Biological Sciences Korea Advanced Institute of Science and Technology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Hyun","family":"Cho","sequence":"additional","affiliation":[{"name":"Biomedical Research Center and Department of Biological Sciences Korea Advanced Institute of Science and Technology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Jeong","family":"Hwang","sequence":"additional","affiliation":[{"name":"Biomedical Research Center and Department of Biological Sciences Korea Advanced Institute of Science and Technology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Ho","family":"Choi","sequence":"additional","affiliation":[{"name":"Biomedical Research Center and Department of Biological Sciences Korea Advanced Institute of Science and Technology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung-Tae","family":"Kim","sequence":"additional","affiliation":[{"name":"Biomedical Research Center and Department of Biological Sciences Korea Advanced Institute of Science and Technology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Young","family":"Ahn","sequence":"additional","affiliation":[{"name":"Biomedical Research Center and Department of Biological Sciences Korea Advanced Institute of Science and Technology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju-Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Biomedical Research Center and Department of Biological Sciences Korea Advanced Institute of Science and Technology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Lark","family":"Oh","sequence":"additional","affiliation":[{"name":"Biomedical Research Center and Department of Biological Sciences Korea Advanced Institute of Science and Technology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyun Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Biomedical Research Center and Department of Biological Sciences Korea Advanced Institute of Science and Technology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gou Young","family":"Koh","sequence":"additional","affiliation":[{"name":"Biomedical Research Center and Department of Biological Sciences Korea Advanced Institute of Science and Technology Daejeon Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,8]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81812-7"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.277.5322.55"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/35025215"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/35067005"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1006\/scdb.2001.0288"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2002.1"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81813-9"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203800"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(00)00231-5"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00217-4"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.5.1904"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65088-2"},{"key":"e_1_2_5_14_1","first-page":"918","article-title":"Angiopoietin-1 is inversely related to thymidine phosphorylase expression in human breast cancer, indicating a role in vascular remodeling","volume":"7","author":"Currie M. 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