Oishi Isao, Suzuki Hiroaki, Onishi Nobuyuki, Takada Ritsuko, Kani Shuichi, Ohkawara Bisei, Koshida Ikue, Suzuki Kentaro, Yamada General, Schwabe Georg C, Mundlos Stefan, Shibuya Hiroshi, Takada Shinji, Minami Yasuhiro
Department of Genome Sciences, Faculty of Medical Sciences, Graduate School of Medicine, Kobe University, Chuo-ku, Kobe 650-0017, Japan.
Genes Cells. 2003 Jul;8(7):645-54. doi: 10.1046/j.1365-2443.2003.00662.x.
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.
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.
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.
Ror2是一种孤儿受体，属于受体酪氨酸激酶的Ror家族。尽管已证明Ror2在发育形态发生中起关键作用，但其介导的精确信号转导事件仍不清楚。由于Ror2具有一个富含半胱氨酸的胞外结构域（CRD），类似于卷曲蛋白（Fz）的Wnt结合位点，因此可以推测Ror2与Wnt家族成员相互作用。
Ror2基因敲除小鼠和Wnt5a基因敲除小鼠均表现出侏儒症、面部异常、四肢和尾巴短小、肺和生殖器发育异常以及室间隔缺损。体外结合试验表明，Wnt5a与Ror2的CRD结合。此外，Ror2通过其CRD与rFz2（一种假定的Wnt5a受体）相关联。有趣的是，通过培养细胞中JNK的激活和非洲爪蟾中会聚延伸运动的抑制评估，Wnt5a和Ror2激活非经典Wnt信号通路。
我们的研究结果表明，Wnt5a与Ror2在物理和功能上相互作用。因此，Ror2可能作为Wnt5a的受体来激活非经典Wnt信号。
