TEK tyrosine kinase explained

Angiopoietin-1 receptor also known as CD202B (cluster of differentiation 202B) is a protein that in humans is encoded by the TEK gene.^{[1] [2]} Also known as TIE2, it is an angiopoietin receptor.

Function

The TEK receptor tyrosine kinase is expressed almost exclusively in endothelial cells in mice, rats, and humans. (TEK is closely related to the TIE receptor tyrosine kinase.)^[3]

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]

In cancer patients, TEK (Tie2) is expressed in a subpopulation of monocytes that home in on the tumor and are essential for the formation of new blood vessels there.^[7]

Interactions

TEK tyrosine kinase has been shown to interact with:

• ANGPT2,
• Angiopoietin 1,^{[8] [9] [10]}
• DOK2.^{[11] [12]}

See also

• Tie-2/Ang-1 signaling

References

Further reading

• Huang L, Turck CW, Rao P, Peters KG . GRB2 and SH-PTP2: potentially important endothelial signaling molecules downstream of the TEK/TIE2 receptor tyrosine kinase . Oncogene . 11 . 10 . 2097–103 . November 1995 . 7478529 .
• Deans JP, Kalt L, Ledbetter JA, Schieven GL, Bolen JB, Johnson P . 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 . September 1995 . 7545683 . 10.1074/jbc.270.38.22632 . free .
• Gallione CJ, Pasyk KA, Boon LM, Lennon F, Johnson DW, Helmbold EA, Markel DS, Vikkula M, Mulliken JB, Warman ML . A gene for familial venous malformations maps to chromosome 9p in a second large kindred . Journal of Medical Genetics . 32 . 3 . 197–9 . March 1995 . 7783168 . 1050316 . 10.1136/jmg.32.3.197 .
• Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, Bieber FR, Morton CC . Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening . Genomics . 23 . 1 . 42–50 . September 1994 . 7829101 . 10.1006/geno.1994.1457 .
• Dumont DJ, Anderson L, Breitman ML, Duncan AM . Assignment of the endothelial-specific protein receptor tyrosine kinase gene (TEK) to human chromosome 9p21 . Genomics . 23 . 2 . 512–3 . September 1994 . 7835909 . 10.1006/geno.1994.1536 .
• Ziegler SF, Bird TA, Schneringer JA, Schooley KA, Baum PR . Molecular cloning and characterization of a novel receptor protein tyrosine kinase from human placenta . Oncogene . 8 . 3 . 663–70 . March 1993 . 8382358 .
• Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, Ryan TE, Bruno J, Radziejewski C, Maisonpierre PC, Yancopoulos GD . Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning . Cell . 87 . 7 . 1161–9 . December 1996 . 8980223 . 10.1016/S0092-8674(00)81812-7 . free .
• Suri C, Jones PF, Patan S, Bartunkova S, Maisonpierre PC, Davis S, Sato TN, Yancopoulos GD . Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis . Cell . 87 . 7 . 1171–80 . December 1996 . 8980224 . 10.1016/S0092-8674(00)81813-9 . free .
• Vikkula M, Boon LM, Carraway KL, Calvert JT, Diamonti AJ, Goumnerov B, Pasyk KA, Marchuk DA, Warman ML, Cantley LC, Mulliken JB, Olsen BR . Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2 . Cell . 87 . 7 . 1181–90 . December 1996 . 8980225 . 10.1016/S0092-8674(00)81814-0 . free .
• Witzenbichler B, Maisonpierre PC, Jones P, Yancopoulos GD, Isner JM . 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 . July 1998 . 9660821 . 10.1074/jbc.273.29.18514 . free .
• Asahara T, Chen D, Takahashi T, Fujikawa K, Kearney M, Magner M, Yancopoulos GD, Isner JM . Tie2 receptor ligands, angiopoietin-1 and angiopoietin-2, modulate VEGF-induced postnatal neovascularization . Circulation Research . 83 . 3 . 233–40 . August 1998 . 9710115 . 10.1161/01.res.83.3.233 . free .
• Sato A, Iwama A, Takakura N, Nishio H, Yancopoulos GD, Suda T . Characterization of TEK receptor tyrosine kinase and its ligands, Angiopoietins, in human hematopoietic progenitor cells . International Immunology . 10 . 8 . 1217–27 . August 1998 . 9723709 . 10.1093/intimm/10.8.1217 . free .
• Jones N, Dumont DJ . The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R . Oncogene . 17 . 9 . 1097–108 . September 1998 . 9764820 . 10.1038/sj.onc.1202115 . 20187169 .
• De Sepulveda P, Okkenhaug K, Rose JL, Hawley RG, Dubreuil P, Rottapel R . Socs1 binds to multiple signalling proteins and suppresses steel factor-dependent proliferation . The EMBO Journal . 18 . 4 . 904–15 . February 1999 . 10022833 . 1171183 . 10.1093/emboj/18.4.904 .
• Valenzuela DM, Griffiths JA, Rojas J, Aldrich TH, Jones PF, Zhou H, McClain J, Copeland NG, Gilbert DJ, Jenkins NA, Huang T, Papadopoulos N, Maisonpierre PC, Davis S, Yancopoulos GD . Angiopoietins 3 and 4: diverging gene counterparts in mice and humans . Proceedings of the National Academy of Sciences of the United States of America . 96 . 5 . 1904–9 . March 1999 . 10051567 . 26709 . 10.1073/pnas.96.5.1904 . 1999PNAS...96.1904V . free .
• 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 . Allelic and locus heterogeneity in inherited venous malformations . Human Molecular Genetics . 8 . 7 . 1279–89 . July 1999 . 10369874 . 10.1093/hmg/8.7.1279 . free .
• Jones N, Master Z, Jones J, Bouchard D, Gunji Y, Sasaki H, Daly R, Alitalo K, Dumont DJ . 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 . October 1999 . 10521483 . 10.1074/jbc.274.43.30896 . free .
• Fachinger G, Deutsch U, Risau W . Functional interaction of vascular endothelial-protein-tyrosine phosphatase with the angiopoietin receptor Tie-2 . Oncogene . 18 . 43 . 5948–53 . October 1999 . 10557082 . 10.1038/sj.onc.1202992 . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Multiple Cutaneous and Mucosal Venous Malformations

Notes and References

1. Partanen J, Armstrong E, Mäkelä TP, Korhonen J, Sandberg M, Renkonen R, Knuutila S, Huebner K, Alitalo K . A novel endothelial cell surface receptor tyrosine kinase with extracellular epidermal growth factor homology domains . Molecular and Cellular Biology . 12 . 4 . 1698–707 . April 1992 . 1312667 . 369613 . 10.1128/mcb.12.4.1698.
2. Boon LM, Mulliken JB, Vikkula M, Watkins H, Seidman J, Olsen BR, Warman ML . Assignment of a locus for dominantly inherited venous malformations to chromosome 9p . Human Molecular Genetics . 3 . 9 . 1583–7 . September 1994 . 7833915 . 10.1093/hmg/3.9.1583 .
3. Web site: Entrez Gene: TEK TEK tyrosine kinase, endothelial (venous malformations, multiple cutaneous and mucosal).
4. Fiedler U, Krissl T, Koidl S, Weiss C, Koblizek T, Deutsch U, Martiny-Baron G, Marmé D, Augustin HG . 6 . 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 . January 2003 . 12427764 . 10.1074/jbc.M208550200 . free .
5. Sakai D, Nakamura Y, Nakai T, Mishima T, Kato S, Grad S, Alini M, Risbud MV, Chan D, Cheah KS, Yamamura K, Masuda K, Okano H, Ando K, Mochida J . 6 . Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc . Nature Communications . 3 . 1264 . 2012 . 23232394 . 3535337 . 10.1038/ncomms2226 . 2012NatCo...3.1264S .
6. Sakai D, Schol J, Bach FC, Tekari A, Sagawa N, Nakamura Y, Chan SC, Nakai T, Creemers LB, Frauchiger DA, May RD, Grad S, Watanabe M, Tryfonidou MA, Gantenbein B . 6 . Successful fishing for nucleus pulposus progenitor cells of the intervertebral disc across species . JOR Spine . 1 . 2 . e1018 . June 2018 . 31463445 . 6686801 . 10.1002/jsp2.1018 . free .
7. Venneri MA, De Palma M, Ponzoni M, Pucci F, Scielzo C, Zonari E, Mazzieri R, Doglioni C, Naldini L . 6 . Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer . Blood . 109 . 12 . 5276–85 . June 2007 . 17327411 . 10.1182/blood-2006-10-053504 . 13999825 . free .
8. Sato A, Iwama A, Takakura N, Nishio H, Yancopoulos GD, Suda T . Characterization of TEK receptor tyrosine kinase and its ligands, Angiopoietins, in human hematopoietic progenitor cells . International Immunology . 10 . 8 . 1217–27 . August 1998 . 9723709 . 10.1093/intimm/10.8.1217 . free .
9. Maisonpierre 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 . Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis . Science . 277 . 5322 . 55–60 . July 1997 . 9204896 . 10.1126/science.277.5322.55 .
10. Davis S, Aldrich TH, Jones PF, Acheson A, Compton DL, Jain V, Ryan TE, Bruno J, Radziejewski C, Maisonpierre PC, Yancopoulos GD . Isolation of angiopoietin-1, a ligand for the TIE2 receptor, by secretion-trap expression cloning . Cell . 87 . 7 . 1161–9 . December 1996 . 8980223 . 10.1016/s0092-8674(00)81812-7 . free .
11. Jones N, Dumont DJ . The Tek/Tie2 receptor signals through a novel Dok-related docking protein, Dok-R . Oncogene . 17 . 9 . 1097–108 . September 1998 . 9764820 . 10.1038/sj.onc.1202115 . 20187169 .
12. Master Z, Jones N, Tran J, Jones J, Kerbel RS, Dumont DJ . Dok-R plays a pivotal role in angiopoietin-1-dependent cell migration through recruitment and activation of Pak . The EMBO Journal . 20 . 21 . 5919–28 . November 2001 . 11689432 . 125712 . 10.1093/emboj/20.21.5919 .