The PDZ protein Canoe/AF-6 links Ras-MAPK, Notch and Wingless/Wnt signaling pathways by directly interacting with Ras, Notch and Dishevelled.
The PDZ protein Canoe/AF-6 links Ras-MAPK, Notch and Wingless/Wnt signaling pathways by directly interacting with Ras, Notch and Dishevelled.
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DOI：
10.1371/journal.pone.0000066
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发表时间：
2006-12-20
期刊：
影响因子：
3.7
通讯作者：
Baylies M
中科院分区：
文献类型：
--
作者：
Carmena A;Speicher S;Baylies M
在过去的几年里，越来越明显的是，信号转导通路不仅仅是线性级联;它们被组织成复杂的信号网络，需要高水平的调控来产生精确和独特的细胞反应。然而，信号通路交叉通信的潜在调控机制仍然知之甚少。在这里，我们表明Ras结合蛋白Canoe（Cno）/AF-6，一种通常与细胞连接相关的PDZ蛋白，是Wingless（Wg）/Wnt，Ras-促分裂原活化蛋白激酶（MAPK）和Notch（N）信号通路交叉通讯的关键调节剂。我们的数据显示Cno/AF-6通过与Ras、N和细胞质蛋白Dishevelled（Dsh）（一种关键的Wg效应物）的物理相互作用对这三种信号传导途径具有抑制作用。我们提出了一个模型，其中CNO，通过这些相互作用，积极协调，在膜水平，Ras-MAPK，N和Wg信号通路在祖细胞规格。
Over the past few years, it has become increasingly apparent that signal transduction pathways are not merely linear cascades; they are organized into complex signaling networks that require high levels of regulation to generate precise and unique cell responses. However, the underlying regulatory mechanisms by which signaling pathways cross-communicate remain poorly understood. Here we show that the Ras-binding protein Canoe (Cno)/AF-6, a PDZ protein normally associated with cellular junctions, is a key modulator of Wingless (Wg)/Wnt, Ras-Mitogen Activated Protein Kinase (MAPK) and Notch (N) signaling pathways cross-communication. Our data show a repressive effect of Cno/AF-6 on these three signaling pathways through physical interactions with Ras, N and the cytoplasmic protein Dishevelled (Dsh), a key Wg effector. We propose a model in which Cno, through those interactions, actively coordinates, at the membrane level, Ras-MAPK, N and Wg signaling pathways during progenitor specification.
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