title: The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway.
abstract: BACKGROUND
  Ror2 is an orphan receptor, belonging to the Ror family of receptor tyrosine kinases. Although Ror2 has been shown to play crucial roles in developmental morphogenesis, the precise signalling events that Ror2 mediates remain elusive. Since Ror2 possesses an extracellular cysteine-rich domain (CRD) that resembles the Wnt-binding sites of the Frizzled (Fz) proteins, it is conceivable that Ror2 interacts with members of the Wnt family.
  
  
  RESULTS
  Both Ror2-/- and Wnt5a-/- mice exhibit dwarfism, facial abnormalities, short limbs and tails, dysplasia of lungs and genitals, and ventricular septal defects. In vitro binding assay revealed that Wnt5a binds to the CRD of Ror2. Furthermore, Ror2 associates via its CRD with rFz2, a putative receptor for Wnt5a. Interestingly, Wnt5a and Ror2 activate the non-canonical Wnt pathway, as assessed by activation of JNK in cultured cells and inhibition of convergent extension movements in Xenopus.
  
  
  CONCLUSIONS
  Our findings indicate that Wnt5a and Ror2 interact physically and functionally. Ror2 may thus act as a receptor for Wnt5a to activate non-canonical Wnt signalling.
authors.affiliation: Department of Genome Sciences, Faculty of Medical Sciences, Graduate School of Medicine, Kobe University, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Oishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Suzuki
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Onishi
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Takada
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kani
authors.forename: Bisei
authors.initials: B
authors.lastname: Ohkawara
authors.forename: Ikue
authors.initials: I
authors.lastname: Koshida
authors.forename: Kentaro
authors.initials: K
authors.lastname: Suzuki
authors.forename: General
authors.initials: G
authors.lastname: Yamada
authors.forename: Georg C
authors.initials: GC
authors.lastname: Schwabe
authors.forename: Stefan
authors.initials: S
authors.lastname: Mundlos
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Shibuya
authors.forename: Shinji
authors.initials: S
authors.lastname: Takada
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Minami
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D010641:Phenotype; D011233:Precipitin Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D015398:Signal Transduction / Q000502:physiology*; D051153:Wnt Proteins; D000071818:Wnt-5a Protein
chemical_list: D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; C477010:Ror2 protein, mouse; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases