The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway
The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway
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DOI：
10.1046/j.1365-2443.2003.00662.x
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发表时间：
2003-07-01
期刊：
影响因子：
2.1
通讯作者：
Minami, Y
中科院分区：
文献类型：
--
作者：
Oishi, I;Suzuki, H;Minami, Y
背景：Ror 2是一种孤儿受体，属于受体酪氨酸激酶Ror家族。虽然Ror 2已被证明在发育形态发生中起着至关重要的作用，但Ror 2介导的精确信号事件仍然难以捉摸。由于Ror 2具有一个细胞外的富含半胱氨酸的结构域（CRD），类似于卷曲（FZ）蛋白的Wnt结合位点，可以想象，Ror 2与Wnt family.Results的成员相互作用：Ror 2（-/-）和Wnt 5a（-/-）小鼠表现出侏儒症，面部畸形，四肢和尾巴短，肺和生殖器发育不良，室间隔缺损。体外结合实验表明Wnt 5a与Ror 2的CRD结合。此外，Ror 2通过其CRD与Wnt 5a的推定受体rFz 2缔合。有趣的是，Wnt 5a和Ror 2激活非经典的Wnt通路，评估JNK在培养的细胞中的激活和收敛的延伸运动在Xenopus .Conclusions抑制：我们的研究结果表明，Wnt 5a和Ror 2相互作用的物理和功能。因此，Ror 2可以作为Wnt 5a的受体来激活非经典Wnt信号传导。
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.