Ding Wei, Warburton David
Developmental Biology Program, Saban Research Institute Childrens Hospital Los Angeles, 4650 Sunset Boulevard, MS 35, Los Angeles, CA 90027, USA.
Biochem Biophys Res Commun. 2008 Oct 24;375(3):460-4. doi: 10.1016/j.bbrc.2008.08.037. Epub 2008 Aug 17.
Mammalian Sprouty2 (Spry2) is a key regulator of the receptor tyrosine kinase/ERK signaling pathway and involved in many biological processes, including cell growth, migration, and tumor suppression. Here, we demonstrated that the intracellular protein level of Spry2 was significantly down-regulated by tumor necrosis factor-alpha (TNF-alpha) in both murine Swiss 3T3 fibroblasts and MLE15 lung epithelial cells. Although TNF-alpha activates multiple signaling cascades, only the inhibitor of p38 MAPK pathway blocked TNF-alpha-induced Spry2 down-regulation. Moreover, since both the mRNA level and protein half-life of Spry2 were unaltered by TNF-alpha treatment, this indicated the possible involvement of a translational mechanism in mediating the inhibitory effect of TNF-alpha. Importantly, rescue of the TNF-alpha-induced down-regulation of Spry2 by gene overexpression led to reverse of the apoptotic effect of TNF-alpha in Swiss 3T3 cells. To our knowledge, this study is the first that reported the association of Spry2 with TNF-alpha signaling pathway.
哺乳动物Sprouty2（Spry2）是受体酪氨酸激酶/ERK信号通路的关键调节因子，参与许多生物学过程，包括细胞生长、迁移和肿瘤抑制。在此，我们证明在小鼠瑞士3T3成纤维细胞和MLE15肺上皮细胞中，肿瘤坏死因子-α（TNF-α）可显著下调Spry2的细胞内蛋白水平。尽管TNF-α激活多种信号级联反应，但只有p38 MAPK通路的抑制剂可阻断TNF-α诱导的Spry2下调。此外，由于TNF-α处理未改变Spry2的mRNA水平和蛋白半衰期，这表明翻译机制可能参与介导TNF-α的抑制作用。重要的是，通过基因过表达挽救TNF-α诱导的Spry2下调可导致瑞士3T3细胞中TNF-α凋亡效应的逆转。据我们所知，本研究是首个报道Spry2与TNF-α信号通路关联的研究。
