Fat/Dachsous Signaling Promotes Drosophila Wing Growth by Regulating the Conformational State of the NDR Kinase Warts.
Fat/Dachsous Signaling Promotes Drosophila Wing Growth by Regulating the Conformational State of the NDR Kinase Warts.
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DOI：
10.1016/j.devcel.2015.11.027
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发表时间：
2015-12-21
影响因子：
11.8
通讯作者：
Struhl G
中科院分区：
文献类型：
--
作者：
Vrabioiu AM;Struhl G
在大多数动物中，核Dbf2相关(NDR)激酶在限制生长中起着核心作用。促进生长的信号在一定程度上是通过抑制STE20/河马蛋白激酶激活NDR激酶来实现的。在这里，我们确定了下调NDR激酶活性的另一种机制。具体地说，我们证明了果蝇NDR激酶疣在发育中的活性取决于它从不活跃的“封闭”构象到由保守的Mps1结合蛋白(Mob)介导的潜在活跃的“开放”构象的转变。此外，我们还证明了原钙粘蛋白Fat和Dachsous之间的信号相互作用，由形态发生者Wingless和Decapentaplecic组织，通过非典型的肌球蛋白Dachs来抑制或逆转这种转变，从而抑制疣。Mats、Fat/Dachsous信号和DAKS对疣构象的调节似乎独立于河马蛋白激酶对疣的磷酸化，从而为通过不同的变构和磷酸化机制控制NDR激酶从而控制生长奠定了先例。
Nuclear Dbf2-related (NDR) kinases play a central role in limiting growth in most animals. Signals that promote growth do so in part by suppressing the activation of NDR kinases by STE20/Hippo kinases. Here, we identify another mechanism for down-regulating NDR kinase activity. Specifically, we show that activity of the Drosophila NDR kinase Warts in the developing wing depends on its transition from an inactive “closed” to a potentially active, “open” conformation mediated by Mats, a conserved Mps1-binder (Mob) protein. Further, we show that signaling interactions between the protocadherins Fat and Dachsous, organized by the morphogens Wingless and Decapentaplegic, suppress Warts by acting via the atypical myosin Dachs to inhibit or reverse this transition. The regulation of Warts conformation by Mats, Fat/Dachsous signaling and Dachs appears independent of Warts phosphorylation by Hippo kinase, establishing a precedent for the control of NDR kinases, and hence growth, by distinct allosteric and phosphorylation mechanisms.