The PTK7 and ROR2 Protein Receptors Interact in the Vertebrate WNT/Planar Cell Polarity (PCP) Pathway *
| Autor: | Virginie Thomé, Anne-Catherine Lhoumeau, Laurent Kodjabachian, Sébastien Martinez, Pierluigi Scerbo, Avais M. Daulat, Jean-Paul Borg, Marilyn Giordano |
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| Přispěvatelé: | Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), BORG, Jean-Paul, Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Embryo
Nonmammalian planar cell polarity [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] Xenopus Proteins migration Biochemistry Receptor tyrosine kinase Xenopus laevis 0302 clinical medicine Cell polarity [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB] Morphogenesis [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Wnt Signaling Pathway ROR2 Orphan receptor 0303 health sciences Wnt signaling pathway Cadherins xenopus PTK7 [SDV.BDD.MOR] Life Sciences [q-bio]/Development Biology/Morphogenesis 3. Good health Cell biology protein-tyrosine kinase (tyrosine kinase) cell polarity 030220 oncology & carcinogenesis WNT5A Tyrosine kinase Active Transport Cell Nucleus Wnt pathway Receptor tyrosine kinase-like orphan receptor [SDV.CAN]Life Sciences [q-bio]/Cancer [SDV.BC]Life Sciences [q-bio]/Cellular Biology Biology Receptor Tyrosine Kinase-like Orphan Receptors Wnt-5a Protein 03 medical and health sciences [SDV.CAN] Life Sciences [q-bio]/Cancer Animals Humans [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry Molecular Biology/Biochemistry [q-bio.BM] Molecular Biology development 030304 developmental biology Cell Nucleus Receptor Protein-Tyrosine Kinases [SDV.BDD.MOR]Life Sciences [q-bio]/Development Biology/Morphogenesis Cell Biology Protocadherins Wnt Proteins body regions HEK293 Cells biology.protein JNK |
| Zdroj: | Journal of Biological Chemistry Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2015, 290 (51), pp.30562-30572. ⟨10.1074/jbc.M115.697615⟩ Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2015, 290 (51), pp.30562-72. ⟨10.1074/jbc.M115.697615⟩ The Journal of Biological Chemistry Journal of Biological Chemistry, 2015, 290 (51), pp.30562-30572. ⟨10.1074/jbc.M115.697615⟩ |
| ISSN: | 0021-9258 1083-351X |
| DOI: | 10.1074/jbc.M115.697615⟩ |
| Popis: | Background: The planar cell polarity pathway plays important roles in morphogenetic processes. Results: PTK7 and ROR2 form a heterodimeric complex and bind to WNT5A, promoting JNK phosphorylation and regulating expression of paraxial protocadherin. Conclusion: PTK7 and ROR2 promote cell movement in mammalian cells and coordinate cell polarity during morphogenetic movements. Significance: We reveal new mechanisms of action of PTK7 in WNT/PCP signaling. 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. |
| Databáze: | OpenAIRE |
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