R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and β-catenin signaling
R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and β-catenin signaling
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DOI：
10.1074/jbc.m701927200
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发表时间：
2007-05-25
影响因子：
4.8
通讯作者：
He, Xi
中科院分区：
文献类型：
--
作者：
Wei, Qiou;Yokota, Chika;He, Xi
R-spondin蛋白是新近鉴定的激活β-连环蛋白信号传导的分泌分子。然而，R-spondin的作用机制及其与Wnt信号的关系仍不清楚。在这里，我们表明，人R-spondin 1（hRspo 1）是一个高亲和力的配体的Wnt共同受体LRP 6（Kd = 1.2 nM）。hRspo 1诱导糖原合成酶激酶3依赖性磷酸化和LRP 6的激活。LRP 6拮抗剂DKK 1抑制hRspo 1诱导的LRP 6磷酸化。我们进一步证明，hRspo 1协同与卷曲5爪蟾轴诱导试验，并诱导磷酸化的Dishevelled，卷曲功能下游的细胞质成分。我们的研究揭示了Wnt和R-spondin信号之间有趣的相似性和区别。
R-spondin proteins are newly identified secreted molecules that activate beta-catenin signaling. However, the mechanism of R-spondin action and its relationship with Wnt signaling remain unclear. Here we show that human R-spondin1 (hRspo1) is a high affinity ligand for the Wnt co-receptor LRP6 (K-d = 1.2 nM). hRspo1 induces glycogen synthase kinase 3-dependent phosphorylation and activation of LRP6. DKK1, an LRP6 antagonist, inhibits hRspo1-induced LRP6 phosphorylation. We further demonstrate that hRspo1 synergizes with Frizzled5 in Xenopus axis induction assays and induces the phosphorylation of Dishevelled, a cytoplasmic component downstream of Frizzled function. Our study reveals interesting similarity and distinction between Wnt and R-spondin signaling.