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マウス Tie2/CD202b/TEK  遺伝子

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    Tie2/CD202b/TEK 背景

    遺伝子の概要: The TEK receptor tyrosine kinase is expressed almost exclusively in endothelial cells in mice, rats, and humans. 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. The ligand for the receptor is angiopoietin-1. 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. TEK is closely related to the TIE receptor tyrosine kinase.
    General information above from NCBI
    触媒活性: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. {ECO:0000255|PROSITE-ProRule:PRU10028, ECO:0000269|PubMed:11513602, ECO:0000269|PubMed:12609966, ECO:0000269|PubMed:14665640, ECO:0000269|PubMed:15851516, ECO:0000269|PubMed:19223473, ECO:0000269|PubMed:8382358}.
    酵素調節: ENZYME REGULATION: Angiopoietin binding leads to receptor dimerization and activation by autophosphorylation at Tyr-992 on the kinase activation loop. Inhibited by staurosporine, K252a, PP2, damnacanthal, SB203580, CEP-11207, CEP-11981 and CE-245677. Inhibited by triazine, thienopyrimidine and thiazolopyrimidine derivatives. {ECO:0000269|PubMed:11080633, ECO:0000269|PubMed:11513602, ECO:0000269|PubMed:17253678, ECO:0000269|PubMed:17350837, ECO:0000269|PubMed:19854647, ECO:0000269|PubMed:20651738}.
    サブユニット構造: Homodimer. Heterodimer with TIE1. Interacts with ANGPT1, ANGPT2 and ANGPT4. At cell-cell contacts in quiescent cells, forms a signaling complex composed of ANGPT1 plus TEK molecules from two adjoining cells. In the absence of endothelial cell-cell contacts, interaction with ANGPT1 mediates contacts with the extracellular matrix. Interacts with PTPRB; this promotes endothelial cell-cell adhesion. Interacts with DOK2, GRB2, GRB7, GRB14, PIK3R1 and PTPN11/SHP2. Colocalizes with DOK2 at contacts with the extracellular matrix in migrating cells. Interacts (tyrosine phosphorylated) with TNIP2. Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain). {ECO:0000269|PubMed:12609966, ECO:0000269|PubMed:14665640, ECO:0000269|PubMed:15284220, ECO:0000269|PubMed:15851516, ECO:0000269|PubMed:16732286, ECO:0000269|PubMed:17253678, ECO:0000269|PubMed:17350837, ECO:0000269|PubMed:18425119, ECO:0000269|PubMed:19451274, ECO:0000269|PubMed:19689429, ECO:0000269|PubMed:19854647, ECO:0000269|PubMed:9204896, ECO:0000269|Ref.32}.
    ドメイン: The soluble extracellular domain is functionally active in angiopoietin binding and can modulate the activity of the membrane-bound form by competing for angiopoietins. {ECO:0000269|PubMed:15284220}.
    細胞内位置: Cell membrane; Single-pass type I membrane protein. Cell junction. Cell junction, focal adhesion. Cytoplasm, cytoskeleton. Secreted. Note=Recruited to cell-cell contacts in quiescent endothelial cells. Colocalizes with the actin cytoskeleton and at actin stress fibers during cell spreading. Recruited to the lower surface of migrating cells, especially the rear end of the cell. Proteolytic processing gives rise to a soluble extracellular domain that is secreted.
    組織特異性: Detected in umbilical vein endothelial cells. Proteolytic processing gives rise to a soluble extracellular domain that is detected in blood plasma (at protein level). Predominantly expressed in endothelial cells and their progenitors, the angioblasts. Has been directly found in placenta and lung, with a lower level in umbilical vein endothelial cells, brain and kidney. {ECO:0000269|PubMed:11806244, ECO:0000269|PubMed:8382358}.
    翻訳後: Proteolytic processing leads to the shedding of the extracellular domain (soluble TIE-2 alias sTIE-2). {ECO:0000269|PubMed:11806244}.; Autophosphorylated on tyrosine residues in response to ligand binding. Autophosphorylation occurs in trans, i.e. one subunit of the dimeric receptor phosphorylates tyrosine residues on the other subunit. Autophosphorylation occurs in a sequential manner, where Tyr-992 in the kinase activation loop is phosphorylated first, followed by autophosphorylation at Tyr-1108 and at additional tyrosine residues. ANGPT1-induced phosphorylation is impaired during hypoxia, due to increased expression of ANGPT2. Phosphorylation is important for interaction with GRB14, PIK3R1 and PTPN11. Phosphorylation at Tyr-1102 is important for interaction with SHC1, GRB2 and GRB7. Phosphorylation at Tyr-1108 is important for interaction with DOK2 and for coupling to downstream signal transduction pathways in endothelial cells. Dephosphorylated by PTPRB. {ECO:0000269|PubMed:11513602, ECO:0000269|PubMed:14665640}.; Ubiquitinated. The phosphorylated receptor is ubiquitinated and internalized, leading to its degradation. {ECO:0000269|PubMed:19689429}.
    疾患関連性: DISEASE: Dominantly inherited venous malformations (VMCM) [MIM:600195]: An error of vascular morphogenesis characterized by dilated, serpiginous channels. {ECO:0000269|PubMed:10369874, ECO:0000269|PubMed:19888299, ECO:0000269|PubMed:8980225}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=May play a role in a range of diseases with a vascular component, including neovascularization of tumors, psoriasis and inflammation.
    シーケンスの類似性: Belongs to the protein kinase superfamily. Tyr protein kinase family. Tie subfamily. {ECO:0000255|PROSITE-ProRule:PRU00159}.; Contains 3 EGF-like domains. {ECO:0000255|PROSITE-ProRule:PRU00076}.; Contains 3 fibronectin type-III domains. {ECO:0000255|PROSITE-ProRule:PRU00316}.; Contains 2 Ig-like C2-type (immunoglobulin-like) domains. {ECO:0000305}.; Contains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
    General information above from UniProt

    TEK, or TIE-2, is an endothelial cell-specific receptor tyrosine kinase (RTK) that is known as a functioning molecule of vascular endothelial cells. TEK comprises a subfamily of RTK with TIE, and these two receptors play critical roles in vascular maturation, maintenance of integrity and remodeling. Targeted mutagenesis of both Tek and its agonistic ligand, Angiopoietin-1, result in embryonic lethality, demonstrating that the signal transduction pathways mediated by this receptor are crucial for normal embryonic development. TEK signaling is indispensable for the development of the embryonic vasculature and suggests that TEK signaling may also be required for the development of the tumor vasculature.

    Tie2/CD202b/TEK 代替名

    Tie2/CD202b/TEK 関連研究

  • Jones N, et al. (1998) The Tek / Tie2 receptor signals through a novel Dok-related docking protein, Dok-R. Oncogene. 17(9): 1097-108.
  • Sato A, et al. (1998) Characterization of TEK receptor tyrosine kinase and its ligands, Angiopoietins, in human hematopoietic progenitor cells. Int Immunol. 10(8): 1217-27.
  • Huang L, et al. (1995) GRB2 and SH-PTP2: potentially important endothelial signaling molecules downstream of the TEK / TIE2 receptor tyrosine kinase. Oncogene. 11(10): 2097-103.
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