The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway.
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.
Oishi
Isao
I
Department of Genome Sciences, Faculty of Medical Sciences, Graduate School of Medicine, Kobe University, Chuo-ku, Kobe 650-0017, Japan.
Suzuki
Hiroaki
H
Onishi
Nobuyuki
N
Takada
Ritsuko
R
Kani
Shuichi
S
Ohkawara
Bisei
B
Koshida
Ikue
I
Suzuki
Kentaro
K
Yamada
General
G
Schwabe
Georg C
GC
Mundlos
Stefan
S
Shibuya
Hiroshi
H
Takada
Shinji
S
Minami
Yasuhiro
Y
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
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