Atlas of Genetics and Cytogenetics in Oncology and Haematology


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TEK (TEK tyrosine kinase, endothelial)

Identity

Other namesCD202B
CD202b
EC 2.7.10.1
hTIE2
p140 TEK
TIE-2
TIE2
VMCM
VMCM1
HGNC (Hugo) TEK
LocusID (NCBI) 7010
Location 9p21.2
Location_base_pair Starts at 27109139 and ends at 27230176 bp from pter ( according to hg19-Feb_2009)  [Mapping]
Note Tie1 and Tie2 [where 'Tie' is an acronym from tyrosine kinase with Ig and EGF homology domains] are the two members of the Tie family of tyrosine kinase receptors. Tie2 has highly conserved sequence across vertebrate species, with greatest amino acid homology occurring in the kinase domain, predominantly express on the surface of endothelial cells. Three secreted natural ligands have been characterized, - Ang1, Ang2 and 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 Tie2 DNA contains 121025 bp, which has 23 coding exons, in plus strand.
Transcription mRNA contains 4817 bp transcribed in centromeric to telomeric orientation; 2 other transcripture structures by alternative splicing have been predicted. The mRNA contains a long (442 bp) 5'-UTR with 5 upstream ORFs and 1 IRES that allows the RNA to be translated under hypoxic conditions.

Protein

Description Tie2 contains 1124 amino acids and belongs to the protein kinase superfamily, Tyr protein kinase family, Tie subfamily. Tie2 receptor contains three epidermal growth factor (EGF)-like domains flanked by three Ig-like (immunoglobulin-like) domains, followed by three fibronectin type-III domains in the extracellular domain. Tie2 possesses one intracellular split tyrosine kinase domain, which is highly conserved between the Tie members sharing a 76% sequence homology. It also contains a single transmembrane domain.
 
Expression TEK/Tie2 is predominantly expressed by vascular endothelial cells: It is detectable in the critical process of new vessels formation during early development, and in the adult in response to cyclic hormonal stimulation in the ovary and uterus, as well as in healing skin wounds. High levels of expression of TEK are found in placenta, lung, spleen, and heart tissues. Hematopoietic stem cells, progenitor and mature pericytes, neural progenitor cells, and a subpopulation of monocytes (Tie2-expressing monocytes) also express Tie2/TEK. In addition, its expression might be induced in response to other pathological conditions as described bellow.
Localisation Cell membrane.
Function TEK/Tie2 is a tyrosine-kinase transmembrane receptor involved in signaling pathways upon stimuli by angiopoietins (natural ligands). It guides the proper patterning of endothelial cells during blood vessel formation and also plays role in vessel remodeling, cell survival, cell migration, and cell-to-matrix and cell-to-cell adhesion. TEK/Tie2 signaling pathway is also involved in Toll-like receptor 2 and integrin signaling.
Homology H. sapiens: TEK;
P. troglodytes: TEK;
B. Taurus: TEK;
M. musculus: Tek;
D. rerio: tie2;
R. novergicus: Tek;
G. gallus: 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 Several somatic mutations have been identified related to non-inherited vascular anomalies:
1) del-Tie2 mutant, consists in an in-frame deletion of 129bp, corresponding to a loss of exon 3 and part of exon 4 (amino acid 122-165 of extracellular Ig-like ligand-binding domain, 43 aa deletion in Ig-like domain);
2) Mutations in exon 17 of TEK/Tie2 in 49,1% (28 of 57 individuals): two somatic TEK mutations (Y897C, R915C) in vascular tumors, and seven somatic TEK mutations in vascular malformations (Y897H, Y897C, L914F, R915C, S917I, R918C, R918H).
In patients with human intramuscular haemangioma, the following Tie2 mutations have been described: G833D, Q837H.

Implicated in

Entity Various cancers
Note Cancer: acute myeloid leukemia and chronic myelogenous leukemia, and solid tumors, such as malignant gliomas, breast cancer, thyroid cancer, gastric cancer, bladder cancer, endometrial carcinoma.
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, Endometrial Adenocarcinoma.
Overexpressed in brain tumor stem cells and leukemic blasts.
Prognosis Correlation of TEK/Tie2 expression and malignancy in Gliomas. Tie2 activation results in increased levels of expression of ABC transporter, and eventually chemoresistance of malignant gliomas. Tie2 regulates migration and invasion of these tumors.
Cellular Tie2 and soluble Tie2 expression might be associated to a higher risk of metastasis in patients with breast and bladder cancer, respectively.
  
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 Systemic sclerosis: microangiopathies
Disease Systemic sclerosis (SSc) is an autoimmune disease characterized by altered angiogenesis that precede fibrosis of skin and internal organs. The abnormal angiogenesis is one of the major causes of microangiopathies.
Prognosis Report suggesting that soluble Tie2 in serum samples from patients with systemic sclerosis is related to the development of vascular abnormalities of this disease (nailfold bleeding and pulmonary arterial hypertension).
Cytogenetics Not determined.
  
Entity Wide range of diseases with a vascular and/or inflammatory component, such as psoriasis, pulmonary hypertension, rheumatoid arthritis
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 Angiopoietin1 have been reported.
Rheumatoid arthritis is characterized by chronic inflammatory changes in synovial tissue and pathological angiogenesis. Tie2 has been shown to be upregulated in synovial tissue of patients with rheumatoid arthritis and to mediate pathological angiogenesis and invasion within affected synovial tissue.
Prognosis Not determined.
Cytogenetics Not determined.
  
Entity Cerebrovascular disease: stroke
Disease In stroke, arterial occlusion of one or more arteries in the brain leads to focal or global ischemia and tissue damage and eventual death. Expression of activated Tie2 and Ang1 lead to enhanced neovascularization, vessel stabilization and improved recovery.
Prognosis Reports suggest that activation of Tie2-mediated pathway is essential in initiation of survival responses in neural progenitor cells against cerebral ischemia and hypoxia.
Cytogenetics Not determined.
  

External links

Nomenclature
HGNC (Hugo)TEK   11724
Cards
AtlasTEKID42517ch9p21
Entrez_Gene (NCBI)TEK  7010  TEK tyrosine kinase, endothelial
GeneCards (Weizmann)TEK
Ensembl (Hinxton)ENSG00000120156 [Gene_View]  chr9:27109139-27230176 [Contig_View]  TEK [Vega]
ICGC DataPortalENSG00000120156
AceView (NCBI)TEK
Genatlas (Paris)TEK
WikiGenes7010
SOURCE (Princeton)NM_000459 NM_001290077 NM_001290078
Genomic and cartography
GoldenPath (UCSC)TEK  -  9p21.2   chr9:27109139-27230176 +  9p21   [Description]    (hg19-Feb_2009)
EnsemblTEK - 9p21 [CytoView]
Mapping of homologs : NCBITEK [Mapview]
OMIM600195   600221   
Gene and transcription
Genbank (Entrez)AB086825 AB208796 AK291775 AK294887 AK295043
RefSeq transcript (Entrez)NM_000459 NM_001290077 NM_001290078
RefSeq genomic (Entrez)AC_000141 NC_000009 NC_018920 NG_011828 NT_008413 NW_001839149 NW_004929342
Consensus coding sequences : CCDS (NCBI)TEK
Cluster EST : UnigeneHs.89640 [ NCBI ]
CGAP (NCI)Hs.89640
Alternative Splicing : Fast-db (Paris)GSHG0030053
Alternative Splicing GalleryENSG00000120156
Gene ExpressionTEK [ NCBI-GEO ]     TEK [ SEEK ]   TEK [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ02763 (Uniprot)
NextProtQ02763  [Medical]
With graphics : InterProQ02763
Splice isoforms : SwissVarQ02763 (Swissvar)
Catalytic activity : Enzyme2.7.10.1 [ Enzyme-Expasy ]   2.7.10.12.7.10.1 [ IntEnz-EBI ]   2.7.10.1 [ BRENDA ]   2.7.10.1 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)EGF_1 (PS00022)    EGF_2 (PS01186)    EGF_3 (PS50026)    FN3 (PS50853)    IG_LIKE (PS50835)    PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_TYR (PS00109)   
Domains : Interpro (EBI)EG-like_dom    EGF-like_CS    Fibronectin_type3    Ig-like_dom    Ig-like_fold    Kinase-like_dom    Prot_kinase_dom    Protein_kinase_ATP_BS    Ser-Thr/Tyr_kinase_cat_dom    Tyr_kin_Tie2_Ig-like_dom-1_N    Tyr_kinase_AS    Tyr_kinase_cat_dom   
Related proteins : CluSTrQ02763
Domain families : Pfam (Sanger)fn3 (PF00041)    Ig_Tie2_1 (PF10430)    Pkinase_Tyr (PF07714)   
Domain families : Pfam (NCBI)pfam00041    pfam10430    pfam07714   
Domain families : Smart (EMBL)EGF (SM00181)  FN3 (SM00060)  TyrKc (SM00219)  
DMDM Disease mutations7010
Blocks (Seattle)Q02763
PDB (SRS)1FVR    2GY5    2GY7    2OO8    2OSC    2P4I    2WQB    3BEA    3L8P    4K0V   
PDB (PDBSum)1FVR    2GY5    2GY7    2OO8    2OSC    2P4I    2WQB    3BEA    3L8P    4K0V   
PDB (IMB)1FVR    2GY5    2GY7    2OO8    2OSC    2P4I    2WQB    3BEA    3L8P    4K0V   
PDB (RSDB)1FVR    2GY5    2GY7    2OO8    2OSC    2P4I    2WQB    3BEA    3L8P    4K0V   
Human Protein AtlasENSG00000120156
Peptide AtlasQ02763
HPRD02571
IPIIPI00412829   IPI00909349   IPI00217492   IPI00979987   IPI01012241   IPI00977089   
Protein Interaction databases
DIP (DOE-UCLA)Q02763
IntAct (EBI)Q02763
FunCoupENSG00000120156
BioGRIDTEK
IntegromeDBTEK
STRING (EMBL)TEK
Ontologies - Pathways
QuickGOQ02763
Ontology : AmiGOangiogenesis  response to hypoxia  stress fiber  positive regulation of protein phosphorylation  positive regulation of protein phosphorylation  endothelial cell proliferation  positive regulation of endothelial cell proliferation  endochondral ossification  sprouting angiogenesis  protein kinase activity  protein tyrosine kinase activity  protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  receptor activity  protein binding  ATP binding  extracellular region  cytoplasm  actin filament  plasma membrane  integral component of plasma membrane  microvillus  cell-cell junction  focal adhesion  cell-matrix adhesion  signal transduction  transmembrane receptor protein tyrosine kinase signaling pathway  cell-cell signaling  heart development  blood coagulation  basal plasma membrane  cell surface  positive regulation of endothelial cell migration  positive regulation of endothelial cell migration  positive regulation of phosphatidylinositol 3-kinase signaling  basolateral plasma membrane  apical plasma membrane  single organismal cell-cell adhesion  negative regulation of angiogenesis  peptidyl-tyrosine phosphorylation  growth factor binding  organ regeneration  regulation of establishment or maintenance of cell polarity  positive regulation of peptidyl-serine phosphorylation  substrate adhesion-dependent cell spreading  intracellular signal transduction  negative regulation of apoptotic process  regulation of vascular permeability  response to peptide hormone  positive regulation of phosphatidylinositol 3-kinase activity  response to estrogen  membrane raft  positive regulation of angiogenesis  positive regulation of angiogenesis  protein autophosphorylation  Tie signaling pathway  negative regulation of inflammatory response  leukocyte migration  protein oligomerization  response to cAMP  positive regulation of focal adhesion assembly  positive regulation of protein kinase B signaling  positive regulation of protein kinase B signaling  definitive hemopoiesis  heart trabecula formation  positive regulation of ERK1 and ERK2 cascade  positive regulation of ERK1 and ERK2 cascade  positive regulation of intracellular signal transduction  positive regulation of actin cytoskeleton reorganization  regulation of endothelial cell apoptotic process  negative regulation of endothelial cell apoptotic process  
Ontology : EGO-EBIangiogenesis  response to hypoxia  stress fiber  positive regulation of protein phosphorylation  positive regulation of protein phosphorylation  endothelial cell proliferation  positive regulation of endothelial cell proliferation  endochondral ossification  sprouting angiogenesis  protein kinase activity  protein tyrosine kinase activity  protein tyrosine kinase activity  transmembrane receptor protein tyrosine kinase activity  receptor activity  protein binding  ATP binding  extracellular region  cytoplasm  actin filament  plasma membrane  integral component of plasma membrane  microvillus  cell-cell junction  focal adhesion  cell-matrix adhesion  signal transduction  transmembrane receptor protein tyrosine kinase signaling pathway  cell-cell signaling  heart development  blood coagulation  basal plasma membrane  cell surface  positive regulation of endothelial cell migration  positive regulation of endothelial cell migration  positive regulation of phosphatidylinositol 3-kinase signaling  basolateral plasma membrane  apical plasma membrane  single organismal cell-cell adhesion  negative regulation of angiogenesis  peptidyl-tyrosine phosphorylation  growth factor binding  organ regeneration  regulation of establishment or maintenance of cell polarity  positive regulation of peptidyl-serine phosphorylation  substrate adhesion-dependent cell spreading  intracellular signal transduction  negative regulation of apoptotic process  regulation of vascular permeability  response to peptide hormone  positive regulation of phosphatidylinositol 3-kinase activity  response to estrogen  membrane raft  positive regulation of angiogenesis  positive regulation of angiogenesis  protein autophosphorylation  Tie signaling pathway  negative regulation of inflammatory response  leukocyte migration  protein oligomerization  response to cAMP  positive regulation of focal adhesion assembly  positive regulation of protein kinase B signaling  positive regulation of protein kinase B signaling  definitive hemopoiesis  heart trabecula formation  positive regulation of ERK1 and ERK2 cascade  positive regulation of ERK1 and ERK2 cascade  positive regulation of intracellular signal transduction  positive regulation of actin cytoskeleton reorganization  regulation of endothelial cell apoptotic process  negative regulation of endothelial cell apoptotic process  
Pathways : KEGGRas signaling pathway    Rap1 signaling pathway    HIF-1 signaling pathway    PI3K-Akt signaling pathway    Rheumatoid arthritis   
REACTOMEQ02763 [protein]
REACTOME PathwaysREACT_604 Hemostasis [pathway]
Protein Interaction DatabaseTEK
Wikipedia pathwaysTEK
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)TEK
SNP (GeneSNP Utah)TEK
SNP : HGBaseTEK
Genetic variants : HAPMAPTEK
1000_GenomesTEK 
ICGC programENSG00000120156 
CONAN: Copy Number AnalysisTEK 
Somatic Mutations in Cancer : COSMICTEK 
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)Vascular Anomaly and Lymphedema Mutation Database
DECIPHER (Syndromes)9:27109139-27230176
Mutations and Diseases : HGMDTEK
OMIM600195    600221   
MedgenTEK
GENETestsTEK
Disease Genetic AssociationTEK
Huge Navigator TEK [HugePedia]  TEK [HugeCancerGEM]
Genomic VariantsTEK  TEK [DGVbeta]
Exome VariantTEK
dbVarTEK
ClinVarTEK
snp3D : Map Gene to Disease7010
General knowledge
Homologs : HomoloGeneTEK
Homology/Alignments : Family Browser (UCSC)TEK
Phylogenetic Trees/Animal Genes : TreeFamTEK
Chemical/Protein Interactions : CTD7010
Chemical/Pharm GKB GenePA36441
Clinical trialTEK
Cancer Resource (Charite)ENSG00000120156
Other databases
Probes
Litterature
PubMed191 Pubmed reference(s) in Entrez
CoreMineTEK
GoPubMedTEK
iHOPTEK

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
 
Structure of the Tie2 RTK domain: self-inhibition by the nucleotide binding loop, activation loop, and C-terminal tail.
Shewchuk LM, Hassell AM, Ellis B, Holmes WD, Davis R, Horne EL, Kadwell SH, McKee DD, Moore JT.
Structure. 2000 Nov 15;8(11):1105-13.
PMID 11080633
 
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
 
Differential expression of the angiogenic Tie receptor family in arthritic and normal synovial tissue.
Shahrara S, Volin MV, Connors MA, Haines GK, Koch AE.
Arthritis Res. 2002;4(3):201-8. Epub 2002 Jan 16.
PMID 12010571
 
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
 
Tie2 receptor tyrosine kinase, a major mediator of tumor necrosis factor alpha-induced angiogenesis in rheumatoid arthritis.
DeBusk LM, Chen Y, Nishishita T, Chen J, Thomas JW, Lin PC.
Arthritis Rheum. 2003 Sep;48(9):2461-71.
PMID 13130465
 
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
 
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 Feb;35(2):150-8.
PMID 14991531
 
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
 
Comparison of the prognosis indication of VEGFR-1 and VEGFR-2 and Tie2 receptor expression in breast carcinoma.
Meunier-Carpentier S, Dales JP, Djemli A, Garcia S, Bonnier P, Andrac-Meyer L, Lavaut MN, Allasia C, Charpin C.
Int J Oncol. 2005 Apr;26(4):977-84.
PMID 15753992
 
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. (REVIEW)
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.
EBS 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
 
Angiogenic factors in normal endometrium and endometrial adenocarcinoma.
Saito M, Sato Y, Watanabe J, Kuramoto H, Kaba S, Fukuda T.
Pathol Int. 2007 Mar;57(3):140-7.
PMID 17295646
 
Treatment of stroke with (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl) amino] diazen-1-ium-1, 2-diolate and bone marrow stromal cells upregulates angiopoietin-1/Tie2 and enhances neovascularization.
Cui X, Chen J, Zacharek A, Roberts C, Savant-Bhonsale S, Chopp M.
Neuroscience. 2008 Sep 22;156(1):155-64. Epub 2008 Jul 18.
PMID 18691637
 
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
 
Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts.
Saharinen P, Eklund L, Miettinen J, Wirkkala R, Anisimov A, Winderlich M, Nottebaum A, Vestweber D, Deutsch U, Koh GY, Olsen BR, Alitalo K.
Nat Cell Biol. 2008 May;10(5):527-37. Epub 2008 Apr 20.
PMID 18425119
 
An Ang1-Tie2-PI3K axis in neural progenitor cells initiates survival responses against oxygen and glucose deprivation.
Bai Y, Meng Z, Cui M, Zhang X, Chen F, Xiao J, Shen L, Zhang Y.
Neuroscience. 2009 May 5;160(2):371-81.
PMID 19409199
 
Increasing Ang1/Tie2 expression by simvastatin treatment induces vascular stabilization and neuroblast migration after stroke.
Chen J, Cui X, Zacharek A, Chopp M.
J Cell Mol Med. 2009 Jul;13(7):1348-57. Epub 2008 Jun 9.
PMID 18544044
 
Nitric oxide donor up-regulation of SDF1/CXCR4 and Ang1/Tie2 promotes neuroblast cell migration after stroke.
Cui X, Chen J, Zacharek A, Roberts C, Yang Y, Chopp M.
J Neurosci Res. 2009 Jan;87(1):86-95.
PMID 18711749
 
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
 
Tie2-mediated multidrug resistance in malignant gliomas is associated with upregulation of ABC transporters.
Martin V, Xu J, Pabbisetty SK, Alonso MM, Liu D, Lee OH, Gumin J, Bhat KP, Colman H, Lang FF, Fueyo J, Gomez-Manzano C.
Oncogene. 2009 Jun 18;28(24):2358-63. Epub 2009 May 4.
PMID 19421150
 
Serum levels of angiogenic factors and their prognostic relevance in bladder cancer.
Szarvas T, Jager T, Droste F, Becker M, Kovalszky I, Romics I, Ergun S, Rubben H.
Pathol Oncol Res. 2009 Jun;15(2):193-201. Epub 2008 Sep 20.
PMID 18807212
 
Tie2/TEK modulates the interaction of glioma and brain tumor stem cells with endothelial cells and promotes an invasive phenotype.
Liu D, Martin V, Fueyo J, Lee OH, Xu J, Cortes-Santiago N, Alonso MM, Aldape K, Colman H, Gomez-Manzano C.
Oncotarget. 2010 Dec;1(8):700-9.
PMID 21321379
 
Do serum angiopoietin-1, angiopoietin-2, and their receptor Tie-2 and 4G/5G variant of PAI-1 gene have a role in the pathogenesis of preeclampsia?
Kamal M, El-Khayat W.
J Investig Med. 2011 Oct;59(7):1147-50.
PMID 21849906
 
Serum Tie2 levels: clinical association with microangiopathies in patients with systemic sclerosis.
Noda S, Asano Y, Aozasa N, Akamata K, Yamada D, Masui Y, Tamaki Z, Kadono T, Sato S.
J Eur Acad Dermatol Venereol. 2011 Dec;25(12):1476-9. doi: 10.1111/j.1468-3083.2011.04012.x. Epub 2011 Mar 2.
PMID 21366713
 
Toll-like receptor 2 induced angiogenesis and invasion is mediated through the Tie2 signalling pathway in rheumatoid arthritis.
Saber T, Veale DJ, Balogh E, McCormick J, NicAnUltaigh S, Connolly M, Fearon U.
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Contributor(s)

Written01-2009Dan Liu, Vanesa Martin, Candelaria Gomez-Manzano
Department Neuro-Oncology and Genetics, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Updated04-2012Mohammad B Hossain, Nahir Cortes-Santiago, Dan Liu, Vanesa Martin, Candelaria Gomez-Manzano
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA (MBH, NCS, DL, VM); Departments of Neuro-Oncology and of Genetics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA (CGM)

Citation

This paper should be referenced as such :
Hossain, MB ; Cortes-Santiago, N ; Liu, D ; Martin, V ; Gomez-Manzano, C
TEK (TEK tyrosine kinase, endothelial)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(9):669-673.
Free online version   Free pdf version   [Bibliographic record ]
History of this paper:
Hossain, MB ; Cortes-Santiago, N ; Liu, D ; Martin, V ; Gomez-Manzano, C. TEK (TEK tyrosine kinase, endothelial). Atlas Genet Cytogenet Oncol Haematol. 2012;16(9):669-673.
http://documents.irevues.inist.fr/bitstream/handle/2042/47539/04-2012-TEKID42517ch9p21.pdf
URL : http://AtlasGeneticsOncology.org/Genes/TEKID42517ch9p21.html

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