© 1997 American Heart Association, Inc.
Articles |
Tie2 Expression and Phosphorylation in Angiogenic and Quiescent Adult Tissues
From the Department of Cell Biology (A.L.W.), the Department of Pathology (Z.A.H., M.W.D., C.S.G.), the Department of Radiation Oncology (M.W.D.), the Department of Medicine, Divisions of Hematology & Medical Oncology (C.S.G.) and the Division of Cardiology (K.G.P.), and the Department of Pharmacology (K.G.P.), Duke University Medical Center, Durham, NC, and the Max-Planck-Institut fur Biochemie (S.W.), Planegg-Marlinsried, Germany.
Correspondence to Dr Kevin G. Peters, Box 3623, Duke University Medical Center, 430 Sands Bldg, Research Drive, Durham, NC 27710. E-mail kgp{at}hodgkin.mc.duke.edu
Abstract Angiogenesis, the process of new vessels sprouting from the existing vasculature, is a critical process during early development. However, angiogenesis rarely occurs in the adult, except in response to cyclic hormonal stimulation in the ovary and uterus, in response to injury, and in response to pathological conditions such as tumorigenesis and diabetes mellitus. Tie2 (also known as Tek) is a novel endothelium-specific receptor tyrosine kinase, which has been demonstrated to be essential for the development of the embryonic vasculature; Tie2 knockout mice die by embryonic day 10.5 with specific defects in the formation of microvessels. Tie2 is downregulated later in embryogenesis, and its function in the adult has been relatively unexplored. To gain insight into the potential functions of Tie2 in the adult vasculature, Tie2 expression was examined in adult tissues undergoing angiogenesis and in quiescent tissues. Tie2 expression was localized by immunohistochemistry to the endothelium of neovessels in rat tissues undergoing angiogenesis during hormonally stimulated follicular maturation and uterine development and in healing skin wounds. Immunoprecipitation and RNase protection assay demonstrated upregulation of Tie2 protein and mRNA in rat and mouse skin wounds, respectively. Moreover, Tie2 immunoprecipitated from skin wounds was tyrosine-phosphorylated, indicating active downstream signaling. Surprisingly, Tie2 was also expressed in the entire spectrum of the quiescent vasculature (arteries, veins, and capillaries) in a wide range of adult tissues, and Tie2 immunoprecipitated from quiescent adult tissues was also tyrosine-phosphorylated. Together, these results suggest a dual function for Tie2 in adult tissues involving both angiogenesis and vascular maintenance.
Key Words: receptor tyrosine kinase • endothelium • angiogenesis • wound healing • Tie2
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H. Beck, T. Acker, C. Wiessner, P. R. Allegrini, and K. H. Plate Expression of Angiopoietin-1, Angiopoietin-2, and Tie Receptors after Middle Cerebral Artery Occlusion in the Rat Am. J. Pathol., November 1, 2000; 157(5): 1473 - 1483. [Abstract] [Full Text] [PDF]
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L. Wyder, A. Vitaliti, H. Schneider, L. W. Hebbard, D. R. Moritz, M. Wittmer, M. Ajmo, and R. Klemenz Increased Expression of H/T-Cadherin in Tumor-penetrating Blood Vessels Cancer Res., September 1, 2000; 60(17): 4682 - 4688. [Abstract] [Full Text]
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C. Willam, P. Koehne, J. S. Jurgensen, M. Grafe, K. D. Wagner, S. Bachmann, U. Frei, and K.-U. Eckardt Tie2 Receptor Expression Is Stimulated by Hypoxia and Proinflammatory Cytokines in Human Endothelial Cells Circ. Res., September 1, 2000; 87(5): 370 - 377. [Abstract] [Full Text] [PDF]
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T. Uchida, M. Nakashima, Y. Hirota, Y. Miyazaki, T. Tsukazaki, and H. Shindo Immunohistochemical localisation of protein tyrosine kinase receptors Tie-1 and Tie-2 in synovial tissue of rheumatoid arthritis: correlation with angiogenesis and synovial proliferation Ann Rheum Dis, August 1, 2000; 59(8): 607 - 614. [Abstract] [Full Text]
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 A. W. Griffioen and G. Molema Angiogenesis: Potentials for Pharmacologic Intervention in the Treatment of Cancer, Cardiovascular Diseases, and Chronic Inflammation Pharmacol. Rev., June 1, 2000; 52(2): 237 - 268. [Abstract] [Full Text] [PDF]
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S. J. Mandriota, C. Pyke, C. Di Sanza, P. Quinodoz, B. Pittet, and M. S. Pepper Hypoxia-Inducible Angiopoietin-2 Expression Is Mimicked by Iodonium Compounds and Occurs in the Rat Brain and Skin in Response to Systemic Hypoxia and Tissue Ischemia Am. J. Pathol., June 1, 2000; 156(6): 2077 - 2089. [Abstract] [Full Text] [PDF]
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K. Hata, R. Fujiwaki, K. Nakayama, M. Fukumoto, and K. Miyazaki Expression of TP and TIE2 genes in normal ovary with corpus luteum and in ovarian cancer: correlation with ultrasound-derived peak systolic velocity Mol. Hum. Reprod., April 1, 2000; 6(4): 319 - 323. [Abstract] [Full Text] [PDF]
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V. EVANS, A. HATZOPOULOS, W. C. AIRD, H. B. RAYBURN, R. D. ROSENBERG, and J. A. KUIVENHOVEN Targeting the Hprt locus in mice reveals differential regulation of Tie2 gene expression in the endothelium Physiol Genomics, March 13, 2000; 2(2): 67 - 75. [Abstract] [Full Text] [PDF]
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N. Jones, Z. Master, J. Jones, D. Bouchard, Y. Gunji, H. Sasaki, R. Daly, K. Alitalo, and D. J. Dumont Identification of Tek/Tie2 Binding Partners. BINDING TO A MULTIFUNCTIONAL DOCKING SITE MEDIATES CELL SURVIVAL AND MIGRATION J. Biol. Chem., October 22, 1999; 274(43): 30896 - 30905. [Abstract] [Full Text] [PDF]
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W. N. Procopio, P. I. Pelavin, W. M. F. Lee, and N. M. Yeilding Angiopoietin-1 and -2 Coiled Coil Domains Mediate Distinct Homo-oligomerization Patterns, but Fibrinogen-like Domains Mediate Ligand Activity J. Biol. Chem., October 15, 1999; 274(42): 30196 - 30201. [Abstract] [Full Text] [PDF]
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A. Otani, H. Takagi, H. Oh, S. Koyama, M. Matsumura, and Y. Honda Expressions of Angiopoietins and Tie2 in Human Choroidal Neovascular Membranes Invest. Ophthalmol. Vis. Sci., August 1, 1999; 40(9): 1912 - 1920. [Abstract] [Full Text] [PDF]
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H. T. YUAN, C. SURI, G. D. YANCOPOULOS, and A. S. WOOLF Expression of Angiopoietin-1, Angiopoietin-2, and the Tie-2 Receptor Tyrosine Kinase during Mouse Kidney Maturation J. Am. Soc. Nephrol., August 1, 1999; 10(8): 1722 - 1736. [Abstract] [Full Text]
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 J. T. Calvert, T. J. Riney, C. D. Kontos, E. H. Cha, V. G. Prieto, C. R. Shea, J. N. Berg, N. C. Nevin, S. A. Simpson, K. A. Pasyk, et al. Allelic and locus heterogeneity in inherited venous malformations Hum. Mol. Genet., July 1, 1999; 8(7): 1279 - 1289. [Abstract] [Full Text] [PDF]
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 J. Holash, P. C. Maisonpierre, D. Compton, P. Boland, C. R. Alexander, D. Zagzag, G. D. Yancopoulos, and S. J. Wiegand Vessel Cooption, Regression, and Growth in Tumors Mediated by Angiopoietins and VEGF Science, June 18, 1999; 284(5422): 1994 - 1998. [Abstract] [Full Text]
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H. Oh, H. Takagi, K. Suzuma, A. Otani, M. Matsumura, and Y. Honda Hypoxia and Vascular Endothelial Growth Factor Selectively Up-regulate Angiopoietin-2 in Bovine Microvascular Endothelial Cells J. Biol. Chem., May 28, 1999; 274(22): 15732 - 15739. [Abstract] [Full Text] [PDF]
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 M. Puri, J Partanen, J Rossant, and A Bernstein Interaction of the TEK and TIE receptor tyrosine kinases during cardiovascular development Development, January 10, 1999; 126(20): 4569 - 4580. [Abstract] [PDF]
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 G. C. Hughes, J. E. Lowe, A. P. Kypson, J. D. St. Louis, A. M. Pippen, K. G. Peters, R. E. Coleman, T. R. DeGrado, C. L. Donovan, B. H. Annex, et al. Neovascularization after transmyocardial laser revascularization in a model of chronic ischemia Ann. Thorac. Surg., December 1, 1998; 66(6): 2029 - 2036. [Abstract] [Full Text] [PDF]
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J. Lauren, Y. Gunji, and K. Alitalo Is Angiopoietin-2 Necessary for the Initiation of Tumor Angiogenesis? Am. J. Pathol., November 1, 1998; 153(5): 1333 - 1339. [Full Text] [PDF]
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A. Stratmann, W. Risau, and K. H. Plate Cell Type-Specific Expression of Angiopoietin-1 and Angiopoietin-2 Suggests a Role in Glioblastoma Angiogenesis Am. J. Pathol., November 1, 1998; 153(5): 1459 - 1466. [Abstract] [Full Text] [PDF]
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W. R. Burfeind Jr, F. G. Duhaylongsod, B. H. Annex, and D. Samuelson High-flow gas insufflation to facilitate MIDCABG: effects on coronary endothelium Ann. Thorac. Surg., October 1, 1998; 66(4): 1246 - 1249. [Abstract] [Full Text] [PDF]
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T. Asahara, D. Chen, T. Takahashi, K. Fujikawa, M. Kearney, M. Magner, G. D. Yancopoulos, and J. M. Isner Tie2 Receptor Ligands, Angiopoietin-1 and Angiopoietin-2, Modulate VEGF-Induced Postnatal Neovascularization Circ. Res., August 10, 1998; 83(3): 233 - 240. [Abstract] [Full Text] [PDF]
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K. G. Peters Vascular Endothelial Growth Factor and the Angiopoietins : Working Together to Build a Better Blood Vessel Circ. Res., August 10, 1998; 83(3): 342 - 343. [Full Text] [PDF]
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P. Lin, J. A. Buxton, A. Acheson, C. Radziejewski, P. C. Maisonpierre, G. D. Yancopoulos, K. M. Channon, L. P. Hale, M. W. Dewhirst, S. E. George, et al. Antiangiogenic gene therapy targeting the endothelium-specific receptor tyrosine kinase Tie2 PNAS, July 21, 1998; 95(15): 8829 - 8834. [Abstract] [Full Text] [PDF]
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C. D. Kontos, T. P. Stauffer, W.-P. Yang, J. D. York, L. Huang, M. A. Blanar, T. Meyer, and K. G. Peters Tyrosine 1101 of Tie2 Is the Major Site of Association of p85 and Is Required for Activation of Phosphatidylinositol 3-Kinase and Akt Mol. Cell. Biol., July 1, 1998; 18(7): 4131 - 4140. [Abstract] [Full Text]
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