WNT 配体拮抗物对 TCF 依赖性信号传导的负调节
中文名称
通路描述
几种不相关的分泌蛋白家族拮抗 WNT 信号传导。分泌的纤毛状相关蛋白（sFRPs）具有富含半胱氨酸的结构域（CRD），该结构域也存在于 FZD 和 ROR 受体中，而 WNT 抑制因子（WIF）蛋白含有 WIF 结构域，该结构域也存在于 WNT 受体 RYK 中。这两类分泌的 WNT 拮抗物通过结合 WNT 并阻止其与 FZD 受体的相互作用来抑制信号传导。sFRPs 也可能能够结合受体，阻断配体结合（Bafico et al, 1999; 综述在 Kawano and Kypta, 2003）。WIF 和 sFRPs 与 WNT 配体相互作用可能在调节 WNT 扩散和梯度形成中发挥作用（综述在 Boloventa et al, 2008）。相比之下，Dickkopf（DKK）和 Sclerostin（SOST）家族成员通过结合 LRP5/6 来拮抗 WNT 信号传导。脊椎动物中有四个 DKK 家族成员；与 DKK1、2 和 4 密切相关的 DKK1、2 和 4 蛋白已被证明在 WNT 信号传导中发挥作用，而更不同的 DKK3 似乎没有（Glinka et al, 1998; Fedi et al, 1999; Mao et al, 2001; Semenov et al, 2001; 综述在 Niehrs, 2006）。分泌的 DKK 蛋白与 LRP6 结合，并与单跨膜蛋白 Kremen 1 和 2 一起，这种相互作用被认为会破坏 WNT 诱导的 FZD-LRP5/6 复合物。在某些情况下，DKK2 也被证明作为 WNT 激动剂发挥作用（综述在 Niehrs, 2006）。
英文描述
Negative regulation of TCF-dependent signaling by WNT ligand antagonists Several unrelated families of secreted proteins antagonize WNT signaling. Secreted frizzled-related proteins (sFRPs) have a cysteine rich domain (CRD) that is also found in FZD and ROR receptors, while WNT inhibitory factor (WIF) proteins contain a WIF domain also present in the WNT-receptor RYK. Both these classes of secreted WNT antagonists inhibit signaling by binding to WNTs and preventing their interaction with the FZD receptors. sFRPs may also able to bind the receptors, blocking ligand binding (Bafico et al, 1999; reviewed in Kawano and Kypta, 2003). The interaction of WIF and sFRPs with WNT ligand may also play a role in regulating WNT diffusion and gradient formation (reviewed in Boloventa et al, 2008).
Dickkopf (DKK) and Sclerostin (SOST) family members, in contrast, antagonize WNT signaling by binding to LRP5/6. There are four DKK family members in vertebrates; the closely related DKK1, 2 and 4 proteins have been shown to have roles in WNT signaling, while the more divergent DKK3 appears not to (Glinka et al, 1998; Fedi et al, 1999; Mao et al, 2001; Semenov et al, 2001; reviewed in Niehrs, 2006). Secreted DKK proteins bind to LRP6 in conjunction with the single-pass transmembrane proteins Kremen 1 and 2, and this interaction is thought to disrupt the WNT-induced FZD-LRP5/6 complex. In some cases, DKK2 has also been shown to function as a WNT agonist (reviewed in N (reviewed in Niehrs, 2006).
Like DKK proteins, SOST binds LRP5/6 and disrupts WNT-dependent receptor activation (Semenov et al, 2005).
Dickkopf (DKK) and Sclerostin (SOST) family members, in contrast, antagonize WNT signaling by binding to LRP5/6. There are four DKK family members in vertebrates; the closely related DKK1, 2 and 4 proteins have been shown to have roles in WNT signaling, while the more divergent DKK3 appears not to (Glinka et al, 1998; Fedi et al, 1999; Mao et al, 2001; Semenov et al, 2001; reviewed in Niehrs, 2006). Secreted DKK proteins bind to LRP6 in conjunction with the single-pass transmembrane proteins Kremen 1 and 2, and this interaction is thought to disrupt the WNT-induced FZD-LRP5/6 complex. In some cases, DKK2 has also been shown to function as a WNT agonist (reviewed in N (reviewed in Niehrs, 2006).
Like DKK proteins, SOST binds LRP5/6 and disrupts WNT-dependent receptor activation (Semenov et al, 2005).
所含基因
11 个基因