C-elegans LIN-18 is a Ryk ortholog in parallel to LIN-17/frizzled in Wnt and functions signaling
C-elegans LIN-18 is a Ryk ortholog in parallel to LIN-17/frizzled in Wnt and functions signaling
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DOI：
10.1016/j.cell.2004.09.001
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发表时间：
2004-09-17
期刊：
影响因子：
64.5
通讯作者：
Sternberg, PW
中科院分区：
文献类型：
--
作者：
Inoue, T;Oz, HS;Sternberg, PW
WNT蛋白是细胞间信号，调节动物发育的各个方面。在秀丽隐杆线虫中，Frizzled型Wnt受体LIN-17和LIN-18的突变影响P7.p外阴血统中的细胞命运模式。我们发现LIN-18编码Ryk/脱轨酪氨酸激酶相关受体家族的成员，最近发现该受体具有Wnt受体的功能。这个家族的成员都有非活性的激酶结构域。LIN-18的激动域是LIN-18功能所必需的，而WNT结合的WIF结构域是必需的。我们还发现Wnt蛋白Lin-44、MoM-2和CWN-2冗余地调节P7.p模式。遗传相互作用表明，LIN-17和LIN-18在平行的途径中相互独立地发挥作用，不同的配体表现出不同的受体特异性。因此，两个独立的Wnt信号通路，一个使用Ryk受体，另一个使用Frizzleed受体，平行地发挥作用，调节线虫外阴的细胞命运模式。
Wnt proteins are intercellular signals that regulate various aspects of animal development. In Caenorhabditis elegans, mutations in lin-17, a Frizzled-class Wnt receptor, and in lin-18 affect cell fate patterning in the P7.p vulval lineage. We found that lin-18 encodes a member of the Ryk/Derailed family of tyrosine kinase-related receptors, recently found to function as Wnt receptors. Members of this family have nonactive kinase domains. The LIN-18 kinase domain is dispensable for LIN-18 function, while the Wnt binding WIF domain is required. We also found that Wnt proteins LIN-44, MOM-2, and CWN-2 redundantly regulate P7.p patterning. Genetic interactions indicate that LIN-17 and LIN-18 function independently of each other in parallel pathways, and different ligands display different receptor specificities. Thus, two independent Wnt signaling pathways, one employing a Ryk receptor and the other a Frizzled receptor, function in parallel to regulate cell fate patterning in the C. elegans vulva.