The PTK7 and ROR2 Protein Receptors Interact in the Vertebrate WNT/Planar Cell Polarity (PCP) Pathway.
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.
From the CRCM, Cell Polarity, Cell Signaling, and Cancer "Equipe Labellisée Ligue Contre le Cancer", INSERM, U1068, 13009 Marseille, France, the Institut Paoli-Calmettes, 13009 Marseille, France, the Aix-Marseille Université, 13284 Marseille, France, the CNRS, UMR7258, 13009 Marseille, France, and.
Sébastien
S
Martinez
the Institut de Biologie du Développement de Marseille, Aix-Marseille Université, CNRS, 13288 Marseille, France.
Pierluigi
P
Scerbo
From the CRCM, Cell Polarity, Cell Signaling, and Cancer "Equipe Labellisée Ligue Contre le Cancer", INSERM, U1068, 13009 Marseille, France, the Institut Paoli-Calmettes, 13009 Marseille, France, the Aix-Marseille Université, 13284 Marseille, France, the CNRS, UMR7258, 13009 Marseille, France, and.
Marilyn
M
Giordano
From the CRCM, Cell Polarity, Cell Signaling, and Cancer "Equipe Labellisée Ligue Contre le Cancer", INSERM, U1068, 13009 Marseille, France, the Institut Paoli-Calmettes, 13009 Marseille, France, the Aix-Marseille Université, 13284 Marseille, France, the CNRS, UMR7258, 13009 Marseille, France, and.
Avais M
AM
Daulat
From the CRCM, Cell Polarity, Cell Signaling, and Cancer "Equipe Labellisée Ligue Contre le Cancer", INSERM, U1068, 13009 Marseille, France, the Institut Paoli-Calmettes, 13009 Marseille, France, the Aix-Marseille Université, 13284 Marseille, France, the CNRS, UMR7258, 13009 Marseille, France, and.
Anne-Catherine
AC
Lhoumeau
the Institut de Biologie du Développement de Marseille, Aix-Marseille Université, CNRS, 13288 Marseille, France.
Virginie
V
Thomé
the Institut de Biologie du Développement de Marseille, Aix-Marseille Université, CNRS, 13288 Marseille, France.
Laurent
L
Kodjabachian
From the CRCM, Cell Polarity, Cell Signaling, and Cancer "Equipe Labellisée Ligue Contre le Cancer", INSERM, U1068, 13009 Marseille, France, the Institut Paoli-Calmettes, 13009 Marseille, France, the Aix-Marseille Université, 13284 Marseille, France, the CNRS, UMR7258, 13009 Marseille, France, and jean-paul.borg@inserm.fr.
Jean-Paul
JP
Borg
D021581:Active Transport, Cell Nucleus; D000818:Animals; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D009024:Morphogenesis / Q000502:physiology; D000091363:Protocadherins; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors / Q000235:genetics / Q000378:metabolism*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000502:physiology*; D000071818:Wnt-5a Protein; D029867:Xenopus Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
D015820:Cadherins; C117635:Pcdh8 protein, Xenopus; D000091363:Protocadherins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C085096:Wnt5a protein, Xenopus; D029867:Xenopus Proteins; C487768:PTK7 protein, Xenopus; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C000598273:Ror2 protein, Xenopus
JNK; PTK7; ROR2; WNT5A; Wnt pathway; cell polarity; development; planar cell polarity; protein-tyrosine kinase (tyrosine kinase)