Atlas of Genetics and Cytogenetics in Oncology and Haematology
TEK (TEK tyrosine kinase, endothelial)
| Identity |
| Other names | CD202B |
| CD202b | |
| EC 2.7.10.1 | |
| OTTHUMP00000021167 | |
| TIE-2 | |
| TIE2 | |
| VMCM | |
| VMCM1 | |
| hTIE2 | |
| HGNC (Hugo) | TEK |
| Location | 9p21.2 |
| Location_base_pair | Starts at 27109147 and ends at 27230171 bp from pter ( according to hg19-Feb_2009) [Mapping] |
| Note | Tyrosine kinase receptor, member of Tie family. Highly conserved sequence across vertebrate species, with greatest amino acid homology occurring in the kinase domain. Its natural ligands are Angiopoietins: ANG1 and ANG2, and the interspecies orthologs Ang3 (mouse) and ANG4 (human). |
| DNA/RNA |
 | |
| Schematic representation of TEK gene, coding region and protein. UTR, untranslated region; Ig, immunoglobulin; EGF, epithelial growth factor. | |
| Description | DNA contains 120887 bp encoding 23 coding exons, in plus strand. |
| Transcription | mRNA contains 4619 bp transcribed in centromeric to telomeric orientation; 2 other transcripture structures by alternative splicing have been predicted. The mRNA contains a long (372 bp) 5'-UTR with 5 upstream ORFs and 1 IRES that allows the RNA to be translated under hypoxic conditions. |
| Protein |
| See Diagram in DNA section. | |
| Description | It contains 1124 aa. It belongs to the protein kinase superfamily, Tyr protein kinase family, Tie subfamily. It contains 3 EGF (epithelial growth factor)-like domains, 3 fibronectin type-III domains, 3 Ig-like (immunoglobulin-like) domains, 1 intracellular tyrosine kinase domain, and a single transmembrane domain. |
| Expression | High level of TEK is found in placenta, lung, spleen and heart tissues. TEK/Tie2 is expressed by endothelial cells. Hematopoietin stem cells, pericytes, monocytes, and certain tumor cells are also reported to express TEK. |
| Localisation | Cell membrane. |
| Function | It is involved in transmembrane receptor protein tyrosine kinase signaling pathway. It may play a role in regulation of angiogenesis, vessel remodeling, cell survival, cell migration, cell-to-matrix and cell-to-cell adhesion. |
| Homology | H. sapiens: TEK; P. troglodytes: TEK; M. musculus: Tek; D. rerio: Tie2; R. novergicus: Tek. |
| Mutations |
| Germinal | Heterozygous TEK substitutions: R849W (10 of 17 families with hereditary mucocutaneous venous malformation, VMCM), Y897S, Y897C, R915H, R918C, V1919L, A925C, K1100N. These mutations result in in vitro ligand-independent hyperphosphorylation. |
| Somatic | Identified in patients (28 of 57 individuals) with sporadic venous malformations: the most frequent are: 1) Del-Tie2 mutant, consists in an in-frame deletion of 129 bp, corresponding to a loss of exon 3 and part of exon 4 (amino acids 122-165 of extracellular Ig-like ligand-binding domain, 43 aa deletion in Ig-like domain); 2) L914F. In patients with human intramuscular haemangioma Tie2 mutations the following mutations have been described: G833D, Q837H. |
| Implicated in |
| Entity | Cancer: Acute Myeloid Leukemia and Chronic Myelogenous Leukemia, and solid tumors, such as Malignant Gliomas, Breast Cancer, Thyroid Cancer, Gastric Cancer. |
| Note | Present in both the vasculature and cancer cells of several solid tumors. |
| Disease | Overexpressed in the vasculature of several tumors, as breast cancer, non-small cell lung cancer, hepatocellular carcinoma, prostate cancer, Kaposi's sarcoma, and astrocytoma. Overexpressed in the cancer cells -outside of the vascular compartment- in Acute and Chronic Myeloid Leukemia, and solid tumors, such as Malignant Astrocytomas, Breast Cancer, Thyroid Cancer, Gastric Cancer. |
| Prognosis | Correlation of TEK/Tie2 expression and malignancy in Gliomas. High Ang2 mRNA expression in peripheral blasts might be an independent favorable prognostic factor for overall survival in AML. |
| Entity | Sporadic and inherited forms of mucocutaneous venous malformations (VMCM) and Intramuscular haemangioma. |
| Disease | Venous malformations are vascular masses composed of dilated channels lined by endothelial cells, with a reduced coverage by pericytes, leading to functionally low resistance vessels. See Mutation section for description of TEK/Tie2 mutations related with these diseases. Some of these mutations affect TEK/Tie2 activity and/or response to ligand. |
| Prognosis | Not determined. |
| Entity | Wide range of diseases with a vascular and/or inflammatory component, such as Psoriasis, Pulmonary hypertension. |
| Disease | Psoriatic lesions are characterized by elongation and dilatation of papillary dermis. Tie2 transgenic mice showed epidermal hyperproliferation, inflammatory cell accumulation, and altered dermal angiogenesis, mimicking the phenotype present in human psoriasis. Pulmonary hypertension is characterized by high pulmonary arterial pressure. Increased levels of activated TEK/Tie2 and ANG1 have been reported. |
| Prognosis | Not determined. |
| Cytogenetics | Not determined. |
| External links |
| Bibliography |
| Vascular dysmorphogenesis caused by an activating mutation in the receptor tyrosine kinase TIE2. |
| Vikkula M, Boon LM, Carraway KL 3rd, Calvert JT, Diamonti AJ, Goumnerov B, Pasyk KA, Marchuk DA, Warman ML, Cantley LC, Mulliken JB, Olsen BR. |
| Cell. 1996 Dec 27;87(7):1181-90. |
| PMID 8980225 |
| Expression of Tie2/Tek in breast tumour vasculature provides a new marker for evaluation of tumour angiogenesis. |
| Peters KG, Coogan A, Berry D, Marks J, Iglehart JD, Kontos CD, Rao P, Sankar S, Trogan E. |
| Br J Cancer. 1998;77(1):51-6. |
| PMID 9459145 |
| Tie receptors: new modulators of angiogenic and lymphangiogenic responses. |
| Jones N, Iljin K, Dumont DJ, Alitalo K. |
| Nat Rev Mol Cell Biol. 2001 Apr;2(4):257-67. (REVIEW) |
| PMID 11283723 |
| Altered expression of angiopoietins and Tie2 endothelium receptor in psoriasis. |
| Kuroda K, Sapadin A, Shoji T, Fleischmajer R, Lebwohl M. |
| J Invest Dermatol. 2001 May;116(5):713-20. |
| PMID 11348459 |
| Tie-2 and angiopoietin-1 expression in human thyroid tumors. |
| Mitsutake N, Namba H, Takahara K, Ishigaki K, Ishigaki J, Ayabe H, Yamashita S. |
| Thyroid. 2002 Feb;12(2):95-9. |
| PMID 11916292 |
| Expression of angiopoietin-1 and its receptor TEK in hematopoietic cells from patients with myeloid leukemia. |
| Muller A, Lange K, Gaiser T, Hofmann M, Bartels H, Feller AC, Merz H.. |
| Leuk Res. 2002 Feb;26(2):163-8. |
| PMID 11755466 |
| Tumor-infiltrating endothelial cells and endothelial precursor cells in inflammatory breast cancer. |
| Shirakawa K, Shibuya M, Heike Y, Takashima S, Watanabe I, Konishi F, Kasumi F, Goldman CK, Thomas KA, Bett A, Terada M, Wakasugi H. |
| Int J Cancer. 2002 May 20;99(3):344-51. |
| PMID 11992402 |
| Signaling molecules in nonfamilial pulmonary hypertension. |
| Du L, Sullivan CC, Chu D, Cho AJ, Kido M, Wolf PL, Yuan JX, Deutsch R, Jamieson SW, Thistlethwaite PA. |
| N Engl J Med. 2003 Feb 6;348(6):500-9 |
| PMID 12571257 |
| Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche. |
| Arai F, Hirao A, Ohmura M, Sato H, Matsuoka S, Takubo K, Ito K, Koh GY, Suda T. |
| Cell. 2004 Jul 23;118(2):149-61. |
| PMID 15260986 |
| Transformation of vascular endothelial cells by a point mutation in the Tie2 gene from human intramuscular haemangioma. |
| Wang H, Zhang Y, Toratani S, Okamoto T. |
| Oncogene. 2004 Nov 11;23(53):8700-4. |
| PMID 15377998 |
| Targeting the Tie2/Tek receptor in astrocytomas. |
| Zadeh G, Qian B, Okhowat A, Sabha N, Kontos CD, Guha A. |
| Am J Pathol. 2004 Feb;164(2):467-76. |
| PMID 14742253 |
| Tie2 identifies a hematopoietic lineage of proangiogenic monocytes required for tumor vessel formation and a mesenchymal population of pericyte progenitors. |
| De Palma M, Venneri MA, Galli R, Sergi Sergi L, Politi LS, Sampaolesi M, Naldini L. |
| Cancer Cell. 2005 Sep;8(3):211-26. |
| PMID 16169466 |
| Analysis of concerted expression of angiogenic growth factors in acute myeloid leukemia: expression of angiopoietin-2 represents an independent prognostic factor for overall survival. |
| Loges S, Heil G, Bruweleit M, Schoder V, Butzal M, Fischer U, Gehling UM, Schuch G, Hossfeld DK, Fiedler W. |
| J Clin Oncol. 2005 Feb 20;23(6):1109-17. |
| PMID 15718307 |
| Expressions and clinical significances of angiopoietin-1, -2 and Tie2 in human gastric cancer. |
| Wang J, Wu K, Zhang D, Tang H, Xie H, Hong L, Pan Y, Lan M, Hu S, Ning X, Fan D. |
| Biochem Biophys Res Commun. 2005 Nov 11;337(1):386-93. |
| PMID 16185665 |
| Tie receptors and their angiopoietin ligands are context-dependent regulators of vascular remodeling. |
| Eklund L, Olsen BR. |
| Exp Cell Res. 2006 Mar 10;312(5):630-41. Epub 2005 Oct 12. |
| PMID 16225862 |
| Expression of the receptor tyrosine kinase Tie2 in neoplastic glial cells is associated with integrin beta1-dependent adhesion to the extracellular matrix. |
| Lee OH, Xu J, Fueyo J, Fuller GN, Aldape KD, Alonso MM, Piao Y, Liu TJ, Lang FF, Bekele BN, Gomez-Manzano C. |
| Mol Cancer Res. 2006 Dec;4(12):915-26. |
| PMID 17189382 |
| Structure of the extracellular domain of Tie receptor tyrosine kinases and localization of the angiopoietin-binding epitope. |
| Macdonald PR, Progias P, Ciani B, Patel S, Mayer U, Steinmetz MO, Kammerer RA. |
| J Biol Chem. 2006 Sep 22;281(38):28408-14. Epub 2006 Jul 18. |
| PMID 16849318 |
| The Tie2 5' untranslated region is inhibitory to 5' end-mediated translation initiation. |
| Park EH, Lee JM, Pelletier J. |
| FEBS Lett. 2006 Feb 20;580(5):1309-19. Epub 2006 Jan 26. |
| PMID 16457819 |
| Expression of angiopoietins and their receptor Tie2 in the bone marrow of patients with acute myeloid leukemia. |
| Schliemann C, Bieker R, Padro T, Kessler T, Hintelmann H, Buchner T, Berdel WE, Mesters RM. |
| Haematologica. 2006 Sep;91(9):1203-11. |
| PMID 16956819 |
| Tie2: a journey from normal angiogenesis to cancer and beyond |
| Martin V, Liu D, Fueyo J, Gomez-Manzano C. |
| Histol Histopathol. 2008 Jun;23(6):773-80. (REVIEW) |
| PMID 18366015 |
| Somatic mutations in angiopoietin receptor gene TEK cause solitary and multiple sporadic venous malformations. |
| Limaye N, Wouters V, Uebelhoer M, Tuominen M, Wirkkala R, Mulliken JB, Eklund L, Boon LM, Vikkula M. |
| Nat Genet. 2009 Jan;41(1):118-24. Epub 2008 Dec 14. |
| PMID 19079259 |
| REVIEW articles | automatic search in PubMed |
| Last year publications | automatic search in PubMed |
| Contributor(s) |
| Written | 01-2009 | Dan Liu, Vanesa Martin, Candelaria Gomez-Manzano |
| Department Neuro-Oncology and Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA |
| Citation |
| This paper should be referenced as such : |
| Liu D, Martin V, Gomez-Manzano C . TEK (TEK tyrosine kinase, endothelial). Atlas Genet Cytogenet Oncol Haematol. January 2009 . URL : http://AtlasGeneticsOncology.org/Genes/TEKID42517ch9p21.html |
| © Atlas of Genetics and Cytogenetics in Oncology and Haematology | indexed on : Thu Jul 15 14:46:29 CEST 2010 |
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