VEGF-mediated signal transduction in lymphatic endothelial cells.
VEGF-mediated signal transduction in lymphatic endothelial cells.
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DOI：
10.1016/j.pathophys.2009.10.004
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发表时间：
2010-09-01
期刊：
影响因子：
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通讯作者：
Claesson-Welsh, Lena
中科院分区：
文献类型：
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作者：
Bahram, Fuad;Claesson-Welsh, Lena
血管生成配体VEGF家族由VEGFA、VEGFB、VEGFC、VEGFD和胎盘生长因子PlGF组成。这些生长因子以重叠模式结合三种酪氨酸受体激酶，分别为VEGFR1、VEGFR2和VEGFR3。最初，VEGFA（原型VEGF）被描述为体外和体内血管内皮细胞生物学的主要调节剂，通过VEGFR2转导其作用。VEGFA、VEGFB和PlGF与VEGFR1结合，至少在胚胎发生期间，VEGFR1是内皮细胞功能的负调节因子。VEGFC和VEGFD被确定为淋巴内皮因子，通过VEGFR3起作用。随着时间的推移，血管内皮生长因子配体在血管生成/淋巴管生成中的作用之间的明确区别已经让位于更复杂的模式。似乎不同的VEGFR2和VEGFR3配体在生物学上有相当广泛的重叠，这两种受体类型都有助于血管生成和淋巴管生成。我们理解的这种范式转变是由于获得了更复杂的试剂和技术，揭示了不同生理和病理条件下配体和受体的动态和塑性表达。此外，对VEGF辅助受体neuropilins在调节对VEGF的反应性中的重要作用的认识改变了我们对VEGF信号转导机制的认识。本文将主要对VEGR3的特性、信号转导及其生物学作用进行综述。
The VEGF family of angiogenic ligands consists of VEGFA, VEGFB, VEGFC, VEGFD and placenta growth factor, PlGF. These growth factors bind in an overlapping pattern to three receptor tyrosine kinases, denoted VEGFR1, VEGFR2 and VEGFR3. Originally, VEGFA (the prototype VEGF) was described as a master regulator of vascular endothelial cell biology in vitro and in vivo, transducing its effect through VEGFR2. VEGFA, VEGFB and PlGF bind to VEGFR1, which is a negative regulator of endothelial cell function at least during embryogenesis. VEGFC and VEGFD were identified as lymphatic endothelial factors, acting via VEGFR3. With time, the very clear distinction between the roles of the VEGF ligands in angiogenesis/lymphangiogenesis has given way for a more complex pattern. It seems that the biology of the different VEGFR2 and VEGFR3 ligands overlaps quite extensively and that both receptor types contribute to angiogenesis as well as lymphangiogenesis. This paradigm shift in our understanding is due to the access to more sophisticated reagents and techniques revealing dynamic and plastic expression of ligands and receptors in different physiological and pathological conditions. Moreover, knowledge on the important role of VEGF coreceptors, the neuropilins, in regulating the responsiveness to VEGF has changed our perception on the mechanism of VEGF signal transduction. This review will primarily focus on the properties of VEGR3, its signal transduction and the resulting biology.