The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

TEK  -  TEK tyrosine kinase, endothelial

Homo sapiens

Synonyms: Angiopoietin-1 receptor, CD202B, CD202b, Endothelial tyrosine kinase, TIE-2, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of TEK


High impact information on TEK

  • (this issue of Cell) demonstrate that HSCs that express the receptor tyrosine kinase Tie2 are quiescent [5].
  • Ang-1, the ligand for Tie2, enhanced the ability of HSCs to become quiescent and also induced their adhesion to bone, protecting them from stresses that suppress hematopoiesis [5].
  • Only one other family of receptor tyrosine kinases, comprising TIE1 and TIE2, is largely endothelial cell specific [6].
  • Although Angiopoietin-1 binds and induces the tyrosine phosphorylation of TIE2, it does not directly promote the growth of cultured endothelial cells [7].
  • A missense mutation resulting in an arginine-to-tryptophan substitution at position 849 in the kinase domain of the receptor tyrosine kinase TIE2 segregates with dominantly inherited VM in two unrelated families [8].

Chemical compound and disease context of TEK


Biological context of TEK


Anatomical context of TEK


Associations of TEK with chemical compounds

  • Herein, we report that Ang1 and Ang2 (1 nM) are both capable of mediating a rapid Tie2 phosphorylation and a rapid, progressive and sustained endothelial PAF synthesis maximal within 4 h (1695% and 851% increase, respectively) [17].
  • The survival effect of high concentration Ang2 was blocked by pre-treatment with soluble Tie2 receptor and the PI 3'-kinase-specific inhibitors, wortmannin and LY294002 [23].
  • No significant associations were observed between the other members of the Ang/Tie2 gene family and patient age, tumor size, lymph node status, tumor grade, vascular invasion, tumor vascularity, vascular maturation, thymidine phosphorylase, or vascular endothelial growth factor A expression (P > 0.05 for all) [9].
  • Cyclical mechanical stretch increased (and Gö6976 or herbimycin A abrogated these increases) the immunohistochemical labelling of angiopoietin-2 and Tie2 receptor after a 6 h stretch [24].
  • Stable interaction between alpha5beta1 integrin and Tie2 tyrosine kinase receptor regulates endothelial cell response to Ang-1 [25].

Physical interactions of TEK


Regulatory relationships of TEK

  • Tie2 was localized in vascularized regions of fibrovascular membranes and was co- expressed with VEGF and factor VIII [31].
  • Together, our results identified a novel interaction between Tie2 with the adapter molecule ShcA and suggested that this interaction may play a role in the regulation of migration and three-dimensional organization of endothelial cells induced by angiopoietin-1 [18].
  • Our results suggest that the autocrine/paracrine signaling of the Ang/Tie2 system is important for the up-regulated angiogenesis in the RA synovium, as well as for synoviocyte behavior, by regulating chemotactic cell movement [32].
  • These findings indicate that the TEK-TEK ligand signaling pathway is regulated in a refined manner and is involved in hematopoietic cell-microenvironment interaction [21].
  • These data suggest that it is endothelial induction of Ang-2 in tumours that regulates vessel stability and supports targeting Tie2 as an effective novel anti-angiogenic therapy in clear cell RCCs [33].

Other interactions of TEK

  • VEGF receptors and Tie2 expression was investigated using immunohistochemical assays with monoclonal antibodies on frozen sections in a series of 918 and 909 patients respectively [34].
  • VEGFR-1 and VEGFR-2 and Tie2 were correlated with long-term (median, 11.3 years) patients' outcome [34].
  • In multivariate analysis (Cox model), VEGFR-1 and Tie2 immunoexpressions were identified as independent prognostic indicators [34].
  • TEK and ACVRL1 could essentially be excluded [35].
  • CONCLUSIONS: In advanced lesions, the activation of the Tie2-mediated STAT5 signaling pathway may negatively regulate vessel growth [27].

Analytical, diagnostic and therapeutic context of TEK


  1. Activation of the tie2 receptor by angiopoietin-1 enhances tumor vessel maturation and impairs squamous cell carcinoma growth. Hawighorst, T., Skobe, M., Streit, M., Hong, Y.K., Velasco, P., Brown, L.F., Riccardi, L., Lange-Asschenfeldt, B., Detmar, M. Am. J. Pathol. (2002) [Pubmed]
  2. Cell type-specific expression of angiopoietin-1 and angiopoietin-2 suggests a role in glioblastoma angiogenesis. Stratmann, A., Risau, W., Plate, K.H. Am. J. Pathol. (1998) [Pubmed]
  3. Potential role of the angiopoietin/tie2 system in ischemia-induced retinal neovascularization. Takagi, H., Koyama, S., Seike, H., Oh, H., Otani, A., Matsumura, M., Honda, Y. Invest. Ophthalmol. Vis. Sci. (2003) [Pubmed]
  4. Expression of the angopoietin-1, angopoietin-2, Tie2, and vascular endothelial growth factor gene in epithelial ovarian cancer. Hata, K., Nakayama, K., Fujiwaki, R., Katabuchi, H., Okamura, H., Miyazaki, K. Gynecol. Oncol. (2004) [Pubmed]
  5. "Tie-ing" down the hematopoietic niche. Moore, K.A., Lemischka, I.R. Cell (2004) [Pubmed]
  6. Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis. Suri, C., Jones, P.F., Patan, S., Bartunkova, S., Maisonpierre, P.C., Davis, S., Sato, T.N., Yancopoulos, G.D. Cell (1996) [Pubmed]
  7. Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning. Davis, S., Aldrich, T.H., Jones, P.F., Acheson, A., Compton, D.L., Jain, V., Ryan, T.E., Bruno, J., Radziejewski, C., Maisonpierre, P.C., Yancopoulos, G.D. Cell (1996) [Pubmed]
  8. Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. Vikkula, M., Boon, L.M., Carraway, K.L., Calvert, J.T., Diamonti, A.J., Goumnerov, B., Pasyk, K.A., Marchuk, D.A., Warman, M.L., Cantley, L.C., Mulliken, J.B., Olsen, B.R. Cell (1996) [Pubmed]
  9. Angiopoietin-1 is inversely related to thymidine phosphorylase expression in human breast cancer, indicating a role in vascular remodeling. Currie, M.J., Gunningham, S.P., Han, C., Scott, P.A., Robinson, B.A., Harris, A.L., Fox, S.B. Clin. Cancer Res. (2001) [Pubmed]
  10. Expression of angiopoietin-1, angiopoietin-2, and Tie2 genes in normal ovary with corpus luteum and in ovarian cancer. Hata, K., Udagawa, J., Fujiwaki, R., Nakayama, K., Otani, H., Miyazaki, K. Oncology (2002) [Pubmed]
  11. Role of angiopoietin-1 in experimental and human pulmonary arterial hypertension. Kugathasan, L., Dutly, A.E., Zhao, Y.D., Deng, Y., Robb, M.J., Keshavjee, S., Stewart, D.J. Chest (2005) [Pubmed]
  12. Angiopoietin decoy secreted at tumor site impairs tumor growth and metastases by inducing local inflammation and altering neoangiogenesis. Melani, C., Stoppacciaro, A., Foroni, C., Felicetti, F., Caré, A., Colombo, M.P. Cancer Immunol. Immunother. (2004) [Pubmed]
  13. Induction of pulmonary hypertension by an angiopoietin 1/TIE2/serotonin pathway. Sullivan, C.C., Du, L., Chu, D., Cho, A.J., Kido, M., Wolf, P.L., Jamieson, S.W., Thistlethwaite, P.A. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  14. Angiopoietin-1 promotes lymphatic sprouting and hyperplasia. Tammela, T., Saaristo, A., Lohela, M., Morisada, T., Tornberg, J., Norrmén, C., Oike, Y., Pajusola, K., Thurston, G., Suda, T., Yla-Herttuala, S., Alitalo, K. Blood (2005) [Pubmed]
  15. Characterization and expression of a novel alternatively spliced human angiopoietin-2. Kim, I., Kim, J.H., Ryu, Y.S., Jung, S.H., Nah, J.J., Koh, G.Y. J. Biol. Chem. (2000) [Pubmed]
  16. Oligomerization and multimerization are critical for angiopoietin-1 to bind and phosphorylate Tie2. Kim, K.T., Choi, H.H., Steinmetz, M.O., Maco, B., Kammerer, R.A., Ahn, S.Y., Kim, H.Z., Lee, G.M., Koh, G.Y. J. Biol. Chem. (2005) [Pubmed]
  17. Angiopoietins-1 and -2 are both capable of mediating endothelial PAF synthesis: Intracellular signalling pathways. Maliba, R., Lapointe, S., Neagoe, P.E., Brkovic, A., Sirois, M.G. Cell. Signal. (2006) [Pubmed]
  18. Adaptor ShcA protein binds tyrosine kinase Tie2 receptor and regulates migration and sprouting but not survival of endothelial cells. Audero, E., Cascone, I., Maniero, F., Napione, L., Arese, M., Lanfrancone, L., Bussolino, F. J. Biol. Chem. (2004) [Pubmed]
  19. Increased Tie2 expression, enhanced response to angiopoietin-1, and dysregulated angiopoietin-2 expression in hemangioma-derived endothelial cells. Yu, Y., Varughese, J., Brown, L.F., Mulliken, J.B., Bischoff, J. Am. J. Pathol. (2001) [Pubmed]
  20. Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2. Witzenbichler, B., Maisonpierre, P.C., Jones, P., Yancopoulos, G.D., Isner, J.M. J. Biol. Chem. (1998) [Pubmed]
  21. Characterization of TEK receptor tyrosine kinase and its ligands, Angiopoietins, in human hematopoietic progenitor cells. Sato, A., Iwama, A., Takakura, N., Nishio, H., Yancopoulos, G.D., Suda, T. Int. Immunol. (1998) [Pubmed]
  22. Human podocytes express angiopoietin 1, a potential regulator of glomerular vascular endothelial growth factor. Satchell, S.C., Harper, S.J., Tooke, J.E., Kerjaschki, D., Saleem, M.A., Mathieson, P.W. J. Am. Soc. Nephrol. (2002) [Pubmed]
  23. Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Kim, I., Kim, J.H., Moon, S.O., Kwak, H.J., Kim, N.G., Koh, G.Y. Oncogene (2000) [Pubmed]
  24. Cyclical mechanical stretch enhances angiopoietin-2 and Tie2 receptor expression in cultured human umbilical vein endothelial cells. Chang, H., Wang, B.W., Kuan, P., Shyu, K.G. Clin. Sci. (2003) [Pubmed]
  25. Stable interaction between alpha5beta1 integrin and Tie2 tyrosine kinase receptor regulates endothelial cell response to Ang-1. Cascone, I., Napione, L., Maniero, F., Serini, G., Bussolino, F. J. Cell Biol. (2005) [Pubmed]
  26. Structure of the angiopoietin-2 receptor binding domain and identification of surfaces involved in Tie2 recognition. Barton, W.A., Tzvetkova, D., Nikolov, D.B. Structure (Camb.) (2005) [Pubmed]
  27. Angiopoietin 2 induces cell cycle arrest in endothelial cells: a possible mechanism involved in advanced plaque neovascularization. Calvi, C., Dentelli, P., Pagano, M., Rosso, A., Pegoraro, M., Giunti, S., Garbarino, G., Camussi, G., Pegoraro, L., Brizzi, M.F. Arterioscler. Thromb. Vasc. Biol. (2004) [Pubmed]
  28. ABIN-2 protects endothelial cells from death and has a role in the antiapoptotic effect of angiopoietin-1. Tadros, A., Hughes, D.P., Dunmore, B.J., Brindle, N.P. Blood (2003) [Pubmed]
  29. Role of the Ets transcription factors in the regulation of the vascular-specific Tie2 gene. Dube, A., Akbarali, Y., Sato, T.N., Libermann, T.A., Oettgen, P. Circ. Res. (1999) [Pubmed]
  30. Angiopoietin-1 inhibits endothelial permeability, neutrophil adherence and IL-8 production. Pizurki, L., Zhou, Z., Glynos, K., Roussos, C., Papapetropoulos, A. Br. J. Pharmacol. (2003) [Pubmed]
  31. Colocalization of Tie2, angiopoietin 2 and vascular endothelial growth factor in fibrovascular membrane from patients with retinopathy of prematurity. Umeda, N., Ozaki, H., Hayashi, H., Miyajima-Uchida, H., Oshima, K. Ophthalmic Res. (2003) [Pubmed]
  32. Autocrine/paracrine role of the angiopoietin-1 and -2/Tie2 system in cell proliferation and chemotaxis of cultured fibroblastic synoviocytes in rheumatoid arthritis. Takahara, K., Iioka, T., Furukawa, K., Uchida, T., Nakashima, M., Tsukazaki, T., Shindo, H. Hum. Pathol. (2004) [Pubmed]
  33. Expression of the angiopoietins and their receptor Tie2 in human renal clear cell carcinomas; regulation by the von Hippel-Lindau gene and hypoxia. Currie, M.J., Gunningham, S.P., Turner, K., Han, C., Scott, P.A., Robinson, B.A., Chong, W., Harris, A.L., Fox, S.B. J. Pathol. (2002) [Pubmed]
  34. Comparison of the prognosis indication of VEGFR-1 and VEGFR-2 and Tie2 receptor expression in breast carcinoma. Meunier-Carpentier, S., Dales, J.P., Djemli, A., Garcia, S., Bonnier, P., Andrac-Meyer, L., Lavaut, M.N., Allasia, C., Charpin, C. Int. J. Oncol. (2005) [Pubmed]
  35. Familial predisposition to tufted angioma: identification of blood and lymphatic vascular components. Tille, J.C., Morris, M.A., Bründler, M.A., Pepper, M.S. Clin. Genet. (2003) [Pubmed]
  36. Proangiogenic properties of human myeloma cells: production of angiopoietin-1 and its potential relationship to myeloma-induced angiogenesis. Giuliani, N., Colla, S., Lazzaretti, M., Sala, R., Roti, G., Mancini, C., Bonomini, S., Lunghi, P., Hojden, M., Genestreti, G., Svaldi, M., Coser, P., Fattori, P.P., Sammarelli, G., Gazzola, G.C., Bataille, R., Almici, C., Caramatti, C., Mangoni, L., Rizzoli, V. Blood (2003) [Pubmed]
  37. Expression of angiopoietin-1 and its receptor TEK in hematopoietic cells from patients with myeloid leukemia. Müller, A., Lange, K., Gaiser, T., Hofmann, M., Bartels, H., Feller, A.C., Merz, H. Leuk. Res. (2002) [Pubmed]
  38. Angiopoietins have distinct modular domains essential for receptor binding, dimerization and superclustering. Davis, S., Papadopoulos, N., Aldrich, T.H., Maisonpierre, P.C., Huang, T., Kovac, L., Xu, A., Leidich, R., Radziejewska, E., Rafique, A., Goldberg, J., Jain, V., Bailey, K., Karow, M., Fandl, J., Samuelsson, S.J., Ioffe, E., Rudge, J.S., Daly, T.J., Radziejewski, C., Yancopoulos, G.D. Nat. Struct. Biol. (2003) [Pubmed]
  39. Tie2 receptor tyrosine kinase, a major mediator of tumor necrosis factor alpha-induced angiogenesis in rheumatoid arthritis. DeBusk, L.M., Chen, Y., Nishishita, T., Chen, J., Thomas, J.W., Lin, P.C. Arthritis Rheum. (2003) [Pubmed]
WikiGenes - Universities