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Tek/Tie2基因敲除小鼠早期血管缺陷的挽救揭示了一种重要的生存功能。

Rescue of the early vascular defects in Tek/Tie2 null mice reveals an essential survival function.

作者信息

Jones N, Voskas D, Master Z, Sarao R, Jones J, Dumont D J

机构信息

Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.

出版信息

EMBO Rep. 2001 May;2(5):438-45. doi: 10.1093/embo-reports/kve093.

DOI:10.1093/embo-reports/kve093
PMID:11375937
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1083887/
Abstract

Disruption of the signaling pathways mediated by the receptor tyrosine kinase Tek/Tie2 has shown that this receptor plays a pivotal role in vascularization of the developing embryo. In this report, we have utilized the tetracycline-responsive binary transgenic system to overcome the early lethal cardiovascular defects associated with the tekDeltasp null allele in order to investigate the role of Tek in later stages of vessel growth. We show for the first time in vivo that synchronized loss of tek expression correlates with rapid endothelial cell apoptosis in hemorrhagic regions of the embryo, demonstrating an ongoing requirement for Tek-mediated signal transduction in vascular maintenance.

摘要

由受体酪氨酸激酶Tek/Tie2介导的信号通路的破坏表明,该受体在发育中胚胎的血管形成中起关键作用。在本报告中,我们利用四环素反应性二元转基因系统来克服与tekDeltasp无效等位基因相关的早期致死性心血管缺陷,以研究Tek在血管生长后期阶段的作用。我们首次在体内表明,tek表达的同步缺失与胚胎出血区域中内皮细胞的快速凋亡相关,这表明在血管维持中持续需要Tek介导的信号转导。

相似文献

1
Rescue of the early vascular defects in Tek/Tie2 null mice reveals an essential survival function.Tek/Tie2基因敲除小鼠早期血管缺陷的挽救揭示了一种重要的生存功能。
EMBO Rep. 2001 May;2(5):438-45. doi: 10.1093/embo-reports/kve093.
2
Dominant-negative and targeted null mutations in the endothelial receptor tyrosine kinase, tek, reveal a critical role in vasculogenesis of the embryo.内皮受体酪氨酸激酶tek中的显性负性突变和靶向无效突变揭示了其在胚胎血管生成中的关键作用。
Genes Dev. 1994 Aug 15;8(16):1897-909. doi: 10.1101/gad.8.16.1897.
3
GRB2 and SH-PTP2: potentially important endothelial signaling molecules downstream of the TEK/TIE2 receptor tyrosine kinase.GRB2和SH-PTP2:TEK/TIE2受体酪氨酸激酶下游潜在重要的内皮信号分子。
Oncogene. 1995 Nov 16;11(10):2097-103.
4
Interaction of the TEK and TIE receptor tyrosine kinases during cardiovascular development.TEK和TIE受体酪氨酸激酶在心血管发育过程中的相互作用。
Development. 1999 Oct;126(20):4569-80. doi: 10.1242/dev.126.20.4569.
5
Tie2 expression and phosphorylation in angiogenic and quiescent adult tissues.成年血管生成组织和静止组织中Tie2的表达与磷酸化
Circ Res. 1997 Oct;81(4):567-74. doi: 10.1161/01.res.81.4.567.
6
Vascularization of the mouse embryo: a study of flk-1, tek, tie, and vascular endothelial growth factor expression during development.小鼠胚胎的血管形成:发育过程中flk-1、tek、tie及血管内皮生长因子表达的研究
Dev Dyn. 1995 May;203(1):80-92. doi: 10.1002/aja.1002030109.
7
Expression of the growth factor progranulin in endothelial cells influences growth and development of blood vessels: a novel mouse model.生长因子颗粒蛋白前体在血管内皮细胞中的表达影响血管的生长和发育:一种新的小鼠模型。
PLoS One. 2013 May 31;8(5):e64989. doi: 10.1371/journal.pone.0064989. Print 2013.
8
The receptor tyrosine kinase TIE is required for integrity and survival of vascular endothelial cells.受体酪氨酸激酶TIE是血管内皮细胞完整性和存活所必需的。
EMBO J. 1995 Dec 1;14(23):5884-91. doi: 10.1002/j.1460-2075.1995.tb00276.x.
9
tek, a novel tyrosine kinase gene located on mouse chromosome 4, is expressed in endothelial cells and their presumptive precursors.
Oncogene. 1992 Aug;7(8):1471-80.
10
Tek/Tie2 signaling: new and old partners.Tek/Tie2信号传导:新老伙伴
Cancer Metastasis Rev. 2000;19(1-2):13-7. doi: 10.1023/a:1026555121511.

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Cell Mol Life Sci. 2022 May 23;79(6):312. doi: 10.1007/s00018-022-04336-9.
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本文引用的文献

1
Angiopoietin-1 regulates endothelial cell survival through the phosphatidylinositol 3'-Kinase/Akt signal transduction pathway.血管生成素-1通过磷脂酰肌醇3'-激酶/蛋白激酶B信号转导途径调节内皮细胞存活。
Circ Res. 2000;86(1):24-9. doi: 10.1161/01.res.86.1.24.
2
Identification of Tek/Tie2 binding partners. Binding to a multifunctional docking site mediates cell survival and migration.Tek/Tie2结合伴侣的鉴定。与多功能对接位点的结合介导细胞存活和迁移。
J Biol Chem. 1999 Oct 22;274(43):30896-905. doi: 10.1074/jbc.274.43.30896.
3
Interaction of the TEK and TIE receptor tyrosine kinases during cardiovascular development.TEK和TIE受体酪氨酸激酶在心血管发育过程中的相互作用。
Development. 1999 Oct;126(20):4569-80. doi: 10.1242/dev.126.20.4569.
4
Conditional transgene expression in endothelial cells.内皮细胞中的条件性转基因表达。
Transgenic Res. 1998 Nov;7(6):421-7. doi: 10.1023/a:1008837410485.
5
Vascular endothelial growth factor regulates endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway. Requirement for Flk-1/KDR activation.血管内皮生长因子通过磷脂酰肌醇3'-激酶/蛋白激酶B信号转导途径调节内皮细胞存活。对Flk-1/KDR激活的需求。
J Biol Chem. 1998 Nov 13;273(46):30336-43. doi: 10.1074/jbc.273.46.30336.
6
TIE1 and TIE2 receptor tyrosine kinases inversely regulate embryonic angiogenesis by the mechanism of intussusceptive microvascular growth.TIE1和TIE2受体酪氨酸激酶通过套叠式微血管生长机制对胚胎血管生成进行反向调节。
Microvasc Res. 1998 Jul;56(1):1-21. doi: 10.1006/mvre.1998.2081.
7
Tyrosine 1101 of Tie2 is the major site of association of p85 and is required for activation of phosphatidylinositol 3-kinase and Akt.Tie2的酪氨酸1101位点是p85结合的主要位点,是磷脂酰肌醇3激酶和Akt激活所必需的。
Mol Cell Biol. 1998 Jul;18(7):4131-40. doi: 10.1128/MCB.18.7.4131.
8
Tie2 expression and phosphorylation in angiogenic and quiescent adult tissues.成年血管生成组织和静止组织中Tie2的表达与磷酸化
Circ Res. 1997 Oct;81(4):567-74. doi: 10.1161/01.res.81.4.567.
9
Angiopoietin-2, a natural antagonist for Tie2 that disrupts in vivo angiogenesis.血管生成素-2,一种Tie2的天然拮抗剂,可破坏体内血管生成。
Science. 1997 Jul 4;277(5322):55-60. doi: 10.1126/science.277.5322.55.
10
Expression and function of murine receptor tyrosine kinases, TIE and TEK, in hematopoietic stem cells.小鼠受体酪氨酸激酶TIE和TEK在造血干细胞中的表达及功能
Blood. 1997 Jun 15;89(12):4317-26.