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.

Research highlights
► ShcA binds to Ror2 in a Wnt-inducible manner.
► Binding of ShcA to Ror2 occurs through the ShcA SH2-domain and a conserved YxLM motif in the Ror2 tyrosine-kinase domain.
► ShcA and Ror2 are co-expressed in dorsal tissues including the spinal chord and cranial nerves in Xenopus embryos.
► ShcA is required for the Wnt-5a/Ror2 mediated regulation of xPAPC expression in gastrulating Xenopus embryos.