Thrombospondin 2 Potentiates Notch3/Jagged1 Signaling
Thrombospondin 2 Potentiates Notch3/Jagged1 Signaling
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DOI：
10.1074/jbc.m803650200
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发表时间：
2009-03-20
影响因子：
4.8
通讯作者：
Wang, Michael M.
中科院分区：
文献类型：
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作者：
Meng, He;Zhang, Xiaojie;Wang, Michael M.
细胞外血栓反应蛋白(TSP或THBS)和Notch跨膜受体家族在多种重叠的细胞功能中发挥作用，并参与发育信号和组织损伤的病理反应。我们证明，TSP2而不是TSP1增强了Notch3信号转导的效力。此外，TSP2以一种依赖Notch配体的方式减少癌细胞的增殖。基因敲除小鼠中TSP2的缺失降低了Notch靶基因的表达。TSP2直接与Notch3和Jagged1结合。TSP1也与Notch3和Jagged1绑定；然而，只有TSP2增强了Notch3和Jagged1之间的相互作用。这些研究表明，TSP2的不同功能还可能包括作为促进跨细胞受体-配体相互作用的中间蛋白的作用。
Extracellular thrombospondins (TSP or THBS) and the Notch family of transmembrane receptors share a role in multiple, overlapping cellular functions and participate in developmental signaling and pathological reactions to tissue injury. We demonstrate that TSP2, but not TSP1, enhances the potency of Notch3 signal transduction. In addition, TSP2 reduces cancer cell proliferation in a Notch-ligand dependent fashion. The loss of TSP2 in knock-out mice reduces Notch target gene expression. TSP2 binds directly to Notch3 and Jagged1. TSP1 also binds to Notch3 and Jagged1; however, only TSP2 augments the interaction between Notch3 and Jagged1. These studies demonstrate that the diverse functions of TSP2 may also include a role as an intermediary protein that facilitates transcellular receptor-ligand interactions.