Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul 05505, Korea.
BMB Rep. 2018 Dec;51(12):636-641. doi: 10.5483/BMBRep.2018.51.12.210.
DPP4 (dipeptidyl peptidase-4), a highly conserved transmembrane glycoprotein with an exo-peptidase activity, has been shown to contribute to glucose metabolism, immune regulation, signal transduction, and cell differentiation. Here, we show that DPP4 is involved in control of activin/nodal signaling in Xenopus early development. In support of this, gain of function of DPP4 augmented Smad2 phosphorylation as well as expression of target genes induced by activin or nodal signal. In addition, Dpp4 and Xnr1 showed synergistic effect on induction of ectopic dorsal body axis, when co-injected at suboptimal doses in early embryos. Conversely, saxagliptin, a DPP4 inhibitor repressed activin induction of Smad2 phosphorylation. Notably, overexpression of Dpp4 disrupted specification of dorsal body axis of embryo, leading to malformed phenotypes such as spina bifida and a shortened and dorsally bent axis. Together, these results suggest that DPP4 functions as a potentiator of activin/nodal signaling pathway. [BMB Reports 2018; 51(12): 636-641].
DPP4（二肽基肽酶-4）是一种高度保守的跨膜糖蛋白，具有外肽酶活性，已被证明有助于葡萄糖代谢、免疫调节、信号转导和细胞分化。在这里，我们表明 DPP4 参与了爪蟾早期发育中激活素/ nodal 信号的控制。支持这一点的是，DPP4 的功能获得增强了 Smad2 磷酸化以及激活素或 nodal 信号诱导的靶基因的表达。此外，当在早期胚胎中以亚最佳剂量共注射时，Dpp4 和 Xnr1 对诱导异位背轴具有协同作用。相反，DPP4 抑制剂 saxagliptin 抑制了激活素诱导的 Smad2 磷酸化。值得注意的是，Dpp4 的过表达破坏了胚胎背轴的特化，导致脊柱裂和缩短且背向弯曲的轴等畸形表型。总之，这些结果表明 DPP4 作为激活素/ nodal 信号通路的增强剂发挥作用。[BMB 报告 2018；51(12)：636-641]。
