Canonical and noncanonical vascular endothelial growth factor pathways: new developments in biology and signal transduction.
Canonical and noncanonical vascular endothelial growth factor pathways: new developments in biology and signal transduction.
复制标题
DOI：
10.1161/atvbaha.114.303215
复制
发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Iruela-Arispe ML
中科院分区：
文献类型：
--
作者：
Domigan CK;Ziyad S;Iruela-Arispe ML
在过去的五年中，我们对VEGF信号的理解有了显著的扩展。特别是，由于认识到异二聚体配体和受体也是信号传导过程的积极参与者，同型二聚体VEGF分子对VEGFR酪氨酸激酶的典型激活过程现在被拓宽了。虽然异二聚体受体在20年前就被描述出来了，但它们的影响，以及额外的细胞表面伴侣和新的自分泌VEGF信号通路的影响，直到现在才开始被阐明。此外，已经确定了通过凝集素和格莱姆林结合以及细胞内活性氧水平升高而发生的非配体独立信号（非规范）。在没有配体的情况下，VEGF受体的激活对专门针对VEGF的治疗方法具有直接意义。本综述简要总结了典型和非典型VEGF信号传导的最新进展，并将这些发现置于其潜在的临床和生物学影响的角度。
The last five years have witnessed a significant expansion in our understanding of VEGF signaling. In particular, the process of canonical activation of VEGFR tyrosine kinases by homodimeric VEGF molecules have now been broadened by the realization that heterodimeric ligands and receptors are also active participants in the signaling process. While heterodimer receptors were described two decades ago, their impact, along with the effect of additional cell surface partners and novel autocrine VEGF signaling pathways, are only now starting to be clarified. Furthermore, ligand-independent signaling (non-canonical) has been identified which occurs through galectin and gremlin binding, and upon rise of intracellular levels of reactive oxygen species. Activation of the VEGF receptors in the absence of ligand holds immediate implications for therapeutic approaches that exclusively target VEGF. The present review provides a concise summary of the recent developments in both canonical and non-canonical VEGF signaling and places these findings in perspective to their potential clinical and biological ramifications.