Abstract
The endothelial receptor tyrosine kinase plays an essential role in vascular development where it is thought to be required for vessel maturation and stabilization. The ligands responsible for activating Tie-1, its signalling pathways and specific cellular functions are however not known. As with some other receptor tyrosine kinases, Tie-1 is subject to extracellular proteolytic cleavage generating a membrane bound receptor fragment comprising the intracellular and transmembrane domains. Here we examine the signalling potential of this Tie-1 endodomain. We show that the Tie-1 endodomain has poor ability to induce tyrosine phosphorylation. However, on formation the endodomain physically associates with a number of tyrosine phosphorylated signalling intermediates including the tyrosine phosphatase and adaptor protein SHP2. The assembly of this multimolecular complex is consistent with the endodomain having a ligand-independent signalling role in the endothelial cell. The potential roles of ectodomain cleavage and cleavage activated signalling in regulating microvessel stability in angiogenesis, vessel remodelling and regression are considered.
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References
Dumont D. J., Yamaguchi T. P., Conlon R. A., Rossant J. and Breitman M. L., 1992, tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors. Oncogene 7: 71–80.
Partanen J., Armstrong E., Makela T. P., Korhonen J., Sandberg M., Renkonen R., et al., 1992, A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains. Mol Cell. Biol. 12: 1698–1707.
Yano M., Iwama A., Nishio H., Suda J., Takada G. and Suda T., 1997, Expression and function of murine receptor tyrosine kinases, TIE and TEK, in hematopoietic stem cells. Blood 89: 4317–4326.
Puri M., Rossant J., Alitalo K., Bernstein A. and Partanen J., 1995, The receptor tyrosine kinase TIE is required for integrity and survival of vascular endothelial cells. EMBOJ. 14: 5884–5891.
Sato T., Tozawa Y., Deutsch U., Wolburg-Bucholz K., Fujiwara Y., Gendron-Maguire M., et al., 1995, Distinct roles of the receptor tyrosine kinases Tie-1 and Tie-2 in blood vessel formation. Nature 376: 70–74.
Davis S., Aldrich T., Jones P., Acheson A., Compton D., Jain V., et al., 1996, Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Cell 87: 1161–1169.
Maisonpierre P. C., Suri C., Jones P. F., Bartunkova S., Weigand S. J., Radziejewski C., et al., 1997, Angiopoietin-2, a natural antagonist for Tie-2 that disrupts in-vivo angiogenesis. Science 277: 55–60.
Valenzuela D. M., Griffiths J. A., Rojas J., Aldrich T. H., Jones P. F., Zhou H., et al., 1999, Angiopoietins 3 and 4: Diverging gene counterparts in mice and humans. Proc. Natl Acad. Sci. (USA) 96: 1904–1909.
Hanahan D., 1997, Signaling vascular morphogenesis and maintenance. Science 211: 48–50.
Huang L., Turck C, Rao P. and Peters K., 1995, GRB2 and SH-PTP2potentially important endothelial signaling molecules downstream of the TEK/TIE2 receptor tyrosine kinase. Oncogene 11: 2097–2103.
Kontos C. D., Stauffer T. P., Yang W.-P., York J. D., Huang L., Blanar M. A., et al., 1998, Tyrosine 1101 of tie-2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt. Mol Cell Biol 18: 4131–4140.
Jones N. and Dumont D. J., 1998, The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R. Oncogene 17: 1097–1108.
Patan S., 1998, TIE1 and TIE2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth. Microvasc Res 56: 1–21.
Heldin C.-H., 1996, Protein tyrosine kinase receptors. Cancer Surv. 27: 7–23.
Yabkowitz R., Myer S., Yanagihara D., Brankow D., Staley T., Elliot G., et al., 1997, Regulation of tie receptor expression on human endothelial cells by protein kinase C-mediated release of soluble tie. Blood 90: 706–715.
Yabkowitz R., Meyer S., Black T., Elliott G., Merewether L. A. and Yamane H. K., 1999, Inflammatory cytokines and vascular endothelial growth factor stimulate the release of soluble tie receptor from human endothelial cells via metalloprotease activation. Blood 93: 1969–1979.
McCarthy M. J., Burrows R., Bell S. C, Christie G., Bell P. R. F. and Brindle N. P. J., 1999, Potential roles of metalloprotease mediated ectodomain cleavage in signaling by the endothelial receptor tyrosine kinase Tie-1. Lab. Invest. 79: in press.
Basler K., Christen B. and Hafen E., 1991, Ligand-independent activation of the sevenless receptor tyrosine kinase changes the fate of cells in the developing Drosophila eye. Cell 64: 1069–1081.
Chantry A., 1995, The kinase domain and membrane localization determine intracellular interactions between epidermal growth factor receptors. J. Biol Chem. 270: 3068–3073.
Rodrigues G. A. and Park M., 1994, Oncogenic activation of tyrosine kinases. Current Opinion in Genetics and Development 4: 15–24.
Freeman R. M. J., Plutzky J. and Neel B. G., 1992, Identification of a human src homology 2-containing protein-tyrosine-phosphatase: a putative homolog of Drosophila corkscrew. Proc. Natl. Acad. Sci. (USA) 89: 11239–11243.
Roche S., McGlade J., Jones M., Gish G. D., Pawson T. and Courtneidge S. A., 1996, Requirement of phospholipase Cgamma, the tyrosine phosphatase Syp and the adaptor proteins She and Nek for PDGF-induced DNA synthesis: Evidence for the existence of Ras-dependent and Ras-independent pathways. EMBO Journal. 15: 4940–4948.
Li W., Nishimura R., Kashishian A., Batzer A. G., Kim W. J. H., Cooper J. A., et al., 1994, A new function for a phosphotyrosine phosphatase: Linking GRB2-Sos to a receptor tyrosine kinase. Molecular & Cellular Biology. 14: 509–517.
Fujioka Y., Matozaki T., Noguchi T., Iwamatsu A., Yamao T., Takahashi N., et al., 1996, A novel membrane glycoprotein, SHPS-1, that binds the SH2-domain-containing protein tyrosine phosphatase SHP-2 in response to mitogens and cell adhesion. Mol. Cell. Biol. 16: 6887–6899.
Vuorela P., Matikainen M. T., Kuusela P., Ylikorkala O., Alitalo K. and Halmesmäki E., 1998, Endothelial tie receptor antigen in maternal and cord blood of healthy and preeclamptic subjects. Obstetrics and Gynecology 92: 179–183.
Beck L. and D’Amore P. A., 1997, Vascular development: cellular and molecular regulation. FASEB J. 11: 365–373.
Benjamin L. E., Hemo I. and Keshet E., 1998, A plasticity window for blood vessel remodelling is defined by pericyte coverage of the preformed endothelial network and is regulated by PDGF-B and VEGF. Development 125: 1591–1598.
Karsan A., Yee E. and Harlan J. M., 1996, Endothelial cell death induced by tumor necrosis factor-alpha is inhibited by the Bcl-2 family member, Al. J. Biol. Chem. 271: 27201–2724.
Spyridopoulos I., Brogi E., Kearney M., Sullivan A. B., Cetrulo C, Isner J. M., et al., 1997, Vascular endothelial growth factor inhibits endothelial cell apoptosis induced by tumor necrosis factor-alpha: balance between growth and death signals [published erratum appears in J Mol Cell Cardiol 1998 Apr;30 (4):897]. J. Mol. Cell. Cardiol. 29: 1321–1330.
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Marron, M.B., Hughes, D.P., McCarthy, M.J., Brindle, N.P.J., Beaumont, E.R. (2000). Tie-1 Receptor Tyrosine Kinase Endodomain Interaction with SHP2: Potential Signalling Mechanisms and Roles in Angiogenesis. In: Maragoudakis, M.E. (eds) Angiogenesis. Advances in Experimental Medicine and Biology, vol 476. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4221-6_3
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DOI: https://doi.org/10.1007/978-1-4615-4221-6_3
Publisher Name: Springer, Boston, MA
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