Controlling Wnt Signaling Specificity and Implications for Targeting WNTs Pharmacologically.
Controlling Wnt Signaling Specificity and Implications for Targeting WNTs Pharmacologically.
复制标题
控制 Wnt 信号传导特异性以及对 WNT 药理学靶向的影响。
DOI：
10.1007/164_2021_529
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发表时间：
2021
影响因子：
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通讯作者：
Willert,Karl
中科院分区：
文献类型：
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作者：
Sonavane,PoojaR;Willert,Karl
Wnt信号对于胚胎的正常发育和成人的组织稳态至关重要。这个信号级联的激活是由分泌的wnt与其受体结合而启动的。由于哺乳动物基因组编码多种Wnt和Wnt受体，该领域的一个长期问题是如何实现Wnt受体特异性。从这些研究中得出的结论是，对Wnt蛋白的产生、分泌、分布和受体相互作用的精细控制，最终导致下游信号级联的激活，控制了无数的生物过程。在这里，我们讨论了调节Wnt蛋白活性的机制，并说明了如何利用多层调节来进行疾病的治疗干预。
Wnt signaling is critical for proper development of the embryo and for tissue homeostasis in the adult. Activation of this signaling cascade is initiated by binding of the secreted Wnts to their receptors. With the mammalian genome encoding multiple Wnts and Wnt receptors, a longstanding question in the field has been how Wnt-receptor specificities are achieved. Emerging from these studies is a picture of exquisite control over Wnt protein production, secretion, distribution, and receptor interactions, culminating in activation of downstream signaling cascades that control a myriad of biological processes. Here we discuss mechanisms by which Wnt protein activities are tuned and illustrate how the multiple layers of regulation can be leveraged for therapeutic interventions in disease.