Wnt5a/Ror2-induced upregulation of xPAPC requires xShcA.

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.