This receptor possesses a unique extracellular domain containing 2 immunoglobulin-like loops separated by 3 epidermal growth factor-like repeats that are connected to 3 fibronectin type III-like repeats.[4] The ligand for the receptor is angiopoietin-1.[3] TEK has also been suggested as a marker for nucleus pulposus progenitor cells, from the intervertebral disc, which upon activation by Angiopoietin-1 starts to multiply and differentiate. [5][6]
Defects in TEK are associated with inherited venous malformations; the TEK signaling pathway appears to be critical for endothelial cell-smooth muscle cell communication in venous morphogenesis.[3]
Interactions
TEK tyrosine kinase has been shown to interact with:
↑Boon LM, Mulliken JB, Vikkula M, Watkins H, Seidman J, Olsen BR, Warman ML (September 1994). "Assignment of a locus for dominantly inherited venous malformations to chromosome 9p". Human Molecular Genetics. 3 (9): 1583–7. doi:10.1093/hmg/3.9.1583. PMID7833915.
↑ 4.04.14.2Fiedler U, Krissl T, Koidl S, Weiss C, Koblizek T, Deutsch U, Martiny-Baron G, Marmé D, Augustin HG (January 2003). "Angiopoietin-1 and angiopoietin-2 share the same binding domains in the Tie-2 receptor involving the first Ig-like loop and the epidermal growth factor-like repeats". The Journal of Biological Chemistry. 278 (3): 1721–7. doi:10.1074/jbc.M208550200. PMID12427764.
↑ 7.07.1Sato A, Iwama A, Takakura N, Nishio H, Yancopoulos GD, Suda T (August 1998). "Characterization of TEK receptor tyrosine kinase and its ligands, Angiopoietins, in human hematopoietic progenitor cells". International Immunology. 10 (8): 1217–27. doi:10.1093/intimm/10.8.1217. PMID9723709.
↑ 8.08.1Maisonpierre PC, Suri C, Jones PF, Bartunkova S, Wiegand SJ, Radziejewski C, Compton D, McClain J, Aldrich TH, Papadopoulos N, Daly TJ, Davis S, Sato TN, Yancopoulos GD (July 1997). "Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis". Science. 277 (5322): 55–60. doi:10.1126/science.277.5322.55. PMID9204896.
↑Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, Ryan TE, Bruno J, Radziejewski C, Maisonpierre PC, Yancopoulos GD (December 1996). "Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning". Cell. 87 (7): 1161–9. doi:10.1016/s0092-8674(00)81812-7. PMID8980223.
↑Jones N, Dumont DJ (September 1998). "The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R". Oncogene. 17 (9): 1097–108. doi:10.1038/sj.onc.1202115. PMID9764820.
Huang L, Turck CW, Rao P, Peters KG (November 1995). "GRB2 and SH-PTP2: potentially important endothelial signaling molecules downstream of the TEK/TIE2 receptor tyrosine kinase". Oncogene. 11 (10): 2097–103. PMID7478529.
Deans JP, Kalt L, Ledbetter JA, Schieven GL, Bolen JB, Johnson P (September 1995). "Association of 75/80-kDa phosphoproteins and the tyrosine kinases Lyn, Fyn, and Lck with the B cell molecule CD20. Evidence against involvement of the cytoplasmic regions of CD20". The Journal of Biological Chemistry. 270 (38): 22632–8. doi:10.1074/jbc.270.38.22632. PMID7545683.
Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, Bieber FR, Morton CC (September 1994). "Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening". Genomics. 23 (1): 42–50. doi:10.1006/geno.1994.1457. PMID7829101.
Dumont DJ, Anderson L, Breitman ML, Duncan AM (September 1994). "Assignment of the endothelial-specific protein receptor tyrosine kinase gene (TEK) to human chromosome 9p21". Genomics. 23 (2): 512–3. doi:10.1006/geno.1994.1536. PMID7835909.
Ziegler SF, Bird TA, Schneringer JA, Schooley KA, Baum PR (March 1993). "Molecular cloning and characterization of a novel receptor protein tyrosine kinase from human placenta". Oncogene. 8 (3): 663–70. PMID8382358.
Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, Ryan TE, Bruno J, Radziejewski C, Maisonpierre PC, Yancopoulos GD (December 1996). "Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning". Cell. 87 (7): 1161–9. doi:10.1016/S0092-8674(00)81812-7. PMID8980223.
Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD (December 1996). "Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis". Cell. 87 (7): 1171–80. doi:10.1016/S0092-8674(00)81813-9. PMID8980224.
Vikkula M, Boon LM, Carraway KL, Calvert JT, Diamonti AJ, Goumnerov B, Pasyk KA, Marchuk DA, Warman ML, Cantley LC, Mulliken JB, Olsen BR (December 1996). "Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2". Cell. 87 (7): 1181–90. doi:10.1016/S0092-8674(00)81814-0. PMID8980225.
Witzenbichler B, Maisonpierre PC, Jones P, Yancopoulos GD, Isner JM (July 1998). "Chemotactic properties of angiopoietin-1 and -2, ligands for the endothelial-specific receptor tyrosine kinase Tie2". The Journal of Biological Chemistry. 273 (29): 18514–21. doi:10.1074/jbc.273.29.18514. PMID9660821.
Asahara T, Chen D, Takahashi T, Fujikawa K, Kearney M, Magner M, Yancopoulos GD, Isner JM (August 1998). "Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization". Circulation Research. 83 (3): 233–40. doi:10.1161/01.res.83.3.233. PMID9710115.
Sato A, Iwama A, Takakura N, Nishio H, Yancopoulos GD, Suda T (August 1998). "Characterization of TEK receptor tyrosine kinase and its ligands, Angiopoietins, in human hematopoietic progenitor cells". International Immunology. 10 (8): 1217–27. doi:10.1093/intimm/10.8.1217. PMID9723709.
Jones N, Dumont DJ (September 1998). "The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R". Oncogene. 17 (9): 1097–108. doi:10.1038/sj.onc.1202115. PMID9764820.
Calvert JT, Riney TJ, Kontos CD, Cha EH, Prieto VG, Shea CR, Berg JN, Nevin NC, Simpson SA, Pasyk KA, Speer MC, Peters KG, Marchuk DA (July 1999). "Allelic and locus heterogeneity in inherited venous malformations". Human Molecular Genetics. 8 (7): 1279–89. doi:10.1093/hmg/8.7.1279. PMID10369874.
Jones N, Master Z, Jones J, Bouchard D, Gunji Y, Sasaki H, Daly R, Alitalo K, Dumont DJ (October 1999). "Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration". The Journal of Biological Chemistry. 274 (43): 30896–905. doi:10.1074/jbc.274.43.30896. PMID10521483.
Fachinger G, Deutsch U, Risau W (October 1999). "Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the angiopoietin receptor Tie-2". Oncogene. 18 (43): 5948–53. doi:10.1038/sj.onc.1202992. PMID10557082.