University Erlangen-Nuremberg, Biology Dept., Developmental Biology Unit, Staudtstr. 5, D-91058 Erlangen, Germany.
Biochem Biophys Res Commun. 2010 Oct 1;400(4):500-6. doi: 10.1016/j.bbrc.2010.08.074. Epub 2010 Aug 21.
Ror receptor-tyrosine kinases act as Wnt-5a receptors in beta-catenin independent Wnt-signaling pathways. In Xenopus, expression of xPAPC is regulated by a Wnt-5a/Ror2 pathway, which resembles typical signaling cascades downstream of receptor-tyrosine kinases. Here, we have identified the phospho-tyrosine binding protein ShcA as an intracellular binding partner of Ror2. ShcA binds to a conserved motif in Ror2 via its SH2-domain. Wnt-5a induces clustering of Ror2 in the cell membrane and recruitment of ShcA to the Ror2 receptor complex. We further show that ShcA is co-expressed with Ror2 in developing Xenopus embryos and ShcA is required for Wnt-5a/Ror2 mediated upregulation of xPAPC, demonstrating the functional relevance of this interaction.
Ror 受体酪氨酸激酶在 β-连环蛋白非依赖性 Wnt 信号通路中充当 Wnt-5a 受体。在非洲爪蟾中，xPAPC 的表达受 Wnt-5a/Ror2 途径的调节，该途径类似于受体酪氨酸激酶下游的典型信号级联反应。在这里，我们已经确定磷酸酪氨酸结合蛋白 ShcA 是 Ror2 的细胞内结合伴侣。ShcA 通过其 SH2 结构域与 Ror2 中的保守基序结合。Wnt-5a 诱导 Ror2 在细胞膜上聚集，并募集 ShcA 到 Ror2 受体复合物。我们进一步表明，ShcA 在发育中的非洲爪蟾胚胎中与 Ror2 共表达，并且 ShcA 是 Wnt-5a/Ror2 介导的 xPAPC 上调所必需的，证明了这种相互作用的功能相关性。
