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XB-ART-51468
J Biol Chem December 18, 2015; 290 (51): 30562-72.

The PTK7 and ROR2 Protein Receptors Interact in the Vertebrate WNT/Planar Cell Polarity (PCP) Pathway.

Martinez S , Scerbo P , Giordano M , Daulat AM , Lhoumeau AC , Thomé V , Kodjabachian L , Borg JP .


Abstract
The non-canonical WNT/planar cell polarity (WNT/PCP) pathway plays important roles in morphogenetic processes in vertebrates. Among WNT/PCP components, protein tyrosine kinase 7 (PTK7) is a tyrosine kinase receptor with poorly defined functions lacking catalytic activity. Here we show that PTK7 associates with receptor tyrosine kinase-like orphan receptor 2 (ROR2) to form a heterodimeric complex in mammalian cells. We demonstrate that PTK7 and ROR2 physically and functionally interact with the non-canonical WNT5A ligand, leading to JNK activation and cell movements. In the Xenopus embryo, Ptk7 functionally interacts with Ror2 to regulate protocadherin papc expression and morphogenesis. Furthermore, we show that Ptk7 is required for papc activation induced by Wnt5a. Interestingly, we find that Wnt5a stimulates the release of the tagged Ptk7 intracellular domain, which can translocate into the nucleus and activate papc expression. This study reveals novel molecular mechanisms of action of PTK7 in non-canonical WNT/PCP signaling that may promote cell and tissue movements.

PubMed ID: 26499793
PMC ID: PMC4683276
Article link: J Biol Chem


Species referenced: Xenopus laevis
Genes referenced: cdc37 ctrl gap43 jun mapk8 myc nectin4 pcdh8 pcdh8.2 ptk7 ror1 ror2 tub wnt1 wnt5a
Morpholinos: ptk7 MO1 ptk7 MO2 ptk7 MO3 ror2 MO2

Phenotypes: Xla Wt + ptk7 MO (fig.4.b) [+]

Article Images: [+] show captions
References [+] :
Angers, Proximal events in Wnt signal transduction. 2009, Pubmed