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Gene Review

TIE1  -  tyrosine kinase with immunoglobulin-like...

Homo sapiens

Synonyms: JTK14, TIE, Tyrosine-protein kinase receptor Tie-1
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Disease relevance of TIE1


High impact information on TIE1

  • In conclusion, we show that Tie1 phosphorylation is induced by multiple angiopoietin proteins and that the activation is amplified via Tie2 [5].
  • Here, we have examined the potential of angiopoietins, ligands for the related Tie2 receptor, to mediate Tie1 activation [5].
  • The Tie1 receptor tyrosine kinase was isolated over a decade ago, but so far no ligand has been found to activate this receptor [5].
  • These results should be important in dissecting the signal transduction pathways and biological functions of Tie1 [5].
  • The Tie1 and Tie2 receptors are expressed by endothelium [3].

Biological context of TIE1


Anatomical context of TIE1


Physical interactions of TIE1

  • This correlates with increased ability of Tie2 to bind ligand after shedding of the Tie1 extracellular domain [11].

Regulatory relationships of TIE1

  • RON and TIE1 were each also expressed in about 35% and JAK2 in about 53% of HL cases [12].

Other interactions of TIE1

  • Levels of Flt1 but not Tie1 correlated with levels of cellular VEGF [2].
  • The levels of angiopoietin-1 and Tie1 receptor proteins, mRNAs and immunohistochemical staining were unaffected by cyclical mechanical stretch [13].
  • In contrast, Tie1 did not interact with ABIN-2 in the yeast two-hybrid system or mammalian cells [14].
  • When Tie2 in HUVECs was prevented from forming heterocomplexes by silencing Tie1 expression, they underwent rapid phosphorylation upon Ang2 treatment, as shown in EPCs [15].
  • We previously reported that Tie1 and Tie2, endothelium-specific tyrosine kinase receptors essential for angiogenesis, are expressed not only by vascular cells, but also by a subpopulation of synovial lining and stromal cells in the inflamed RA synovium [16].


  1. NERF2, a member of the Ets family of transcription factors, is increased in response to hypoxia and angiopoietin-1: a potential mechanism for Tie2 regulation during hypoxia. Christensen, R.A., Fujikawa, K., Madore, R., Oettgen, P., Varticovski, L. J. Cell. Biochem. (2002) [Pubmed]
  2. Clinical relevance of Flt1 and Tie1 angiogenesis receptors expression in B-cell chronic lymphocytic leukemia (CLL). Aguayo, A., Manshouri, T., O'Brien, S., Keating, M., Beran, M., Koller, C., Kantarjian, H., Rogers, A., Albitar, M. Leuk. Res. (2001) [Pubmed]
  3. Expression of Tie1, Tie2, and angiopoietins 1, 2, and 4 in Kaposi's sarcoma and cutaneous angiosarcoma. Brown, L.F., Dezube, B.J., Tognazzi, K., Dvorak, H.F., Yancopoulos, G.D. Am. J. Pathol. (2000) [Pubmed]
  4. Expression and functional significance of VE-cadherin in aggressive human melanoma cells: role in vasculogenic mimicry. Hendrix, M.J., Seftor, E.A., Meltzer, P.S., Gardner, L.M., Hess, A.R., Kirschmann, D.A., Schatteman, G.C., Seftor, R.E. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  5. Multiple angiopoietin recombinant proteins activate the Tie1 receptor tyrosine kinase and promote its interaction with Tie2. Saharinen, P., Kerkelä, K., Ekman, N., Marron, M., Brindle, N., Lee, G.M., Augustin, H., Koh, G.Y., Alitalo, K. J. Cell Biol. (2005) [Pubmed]
  6. Distinct rat genes with related profiles of expression define a TIE receptor tyrosine kinase family. Maisonpierre, P.C., Goldfarb, M., Yancopoulos, G.D., Gao, G. Oncogene (1993) [Pubmed]
  7. Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue. Shahrara, S., Volin, M.V., Connors, M.A., Haines, G.K., Koch, A.E. Arthritis Res. (2002) [Pubmed]
  8. Identification of receptor genes in renal cell carcinoma associated with angiogenesis by differential hybridization technique. Takahashi, A., Sasaki, H., Kim, S.J., Kakizoe, T., Miyao, N., Sugimura, T., Terada, M., Tsukamoto, T. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  9. Expression of tie1 and tie2 proteins during reendothelialization in balloon-injured rat carotid artery. Fujikawa, K., Presman, E., Isner, J.M., Varticovski, L. J. Vasc. Res. (1999) [Pubmed]
  10. Growth factor signaling pathways in vascular development. Tallquist, M.D., Soriano, P., Klinghoffer, R.A. Oncogene (1999) [Pubmed]
  11. Regulated proteolytic processing of Tie1 modulates ligand responsiveness of the receptor-tyrosine kinase Tie2. Marron, M.B., Singh, H., Tahir, T.A., Kavumkal, J., Kim, H.Z., Koh, G.Y., Brindle, N.P. J. Biol. Chem. (2007) [Pubmed]
  12. High expression of several tyrosine kinases and activation of the PI3K/AKT pathway in mediastinal large B cell lymphoma reveals further similarities to Hodgkin lymphoma. Renné, C., Willenbrock, K., Martin-Subero, J.I., Hinsch, N., Döring, C., Tiacci, E., Klapper, W., Möller, P., Küppers, R., Hansmann, M.L., Siebert, R., Bräuninger, A. Leukemia (2007) [Pubmed]
  13. 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]
  14. The antiinflammatory endothelial tyrosine kinase Tie2 interacts with a novel nuclear factor-kappaB inhibitor ABIN-2. Hughes, D.P., Marron, M.B., Brindle, N.P. Circ. Res. (2003) [Pubmed]
  15. Interaction between Tie receptors modulates angiogenic activity of angiopoietin2 in endothelial progenitor cells. Kim, K.L., Shin, I.S., Kim, J.M., Choi, J.H., Byun, J., Jeon, E.S., Suh, W., Kim, D.K. Cardiovasc. Res. (2006) [Pubmed]
  16. 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]
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