TY - JOUR
T1 - R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and β-catenin signaling
AU - Wei, Qiou
AU - Yokota, Chika
AU - Semenov, Mikhail V.
AU - Doble, Brad
AU - Woodgett, Jim
AU - He, Xi
PY - 2007/5/25
Y1 - 2007/5/25
N2 - R-spondin proteins are newly identified secreted molecules that activate β-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 (Kd = 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.
AB - R-spondin proteins are newly identified secreted molecules that activate β-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 (Kd = 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.
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U2 - 10.1074/jbc.M701927200
DO - 10.1074/jbc.M701927200
M3 - Article
C2 - 17400545
AN - SCOPUS:34447526784
SN - 0021-9258
VL - 282
SP - 15903
EP - 15911
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 21
ER -