Tao-1 phosphorylates Hippo/MST kinases to regulate the Hippo-Salvador-Warts tumor suppressor pathway.

Tao-1 phosphorylates Hippo/MST kinases to regulate the Hippo-Salvador-Warts tumor suppressor pathway.
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DOI:
10.1016/j.devcel.2011.08.028
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发表时间:
2011-11-15
期刊:
影响因子:
11.8
通讯作者:
Fehon, Richard G.
Fehon, Richard G.
中科院分区:
生物学1区
文献类型:
--
作者:
Boggiano, Julian C.;Vanderzalm, Pamela J.;Fehon, Richard G.

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最近的研究表明,Hippo-Salvador-Warts(HSW)途径通过磷酸化和灭活癌蛋白Yorkie来抑制组织生长。生长抑制信号如何在Hippo上游转导仍不清楚。我们表明,不育20家族激酶,陶-1,直接磷酸化T195在河马激活环,像其他HSW途径基因,陶-1的功能,以限制细胞增殖发育中的成虫上皮细胞。这种关系似乎是进化保守的,因为哺乳动物的Tao-1同样影响MST激酶。在S2细胞中,Tao-1介导上游HSW组分Merlin和Expanded的作用,这与Tao-1在组织中调节Hippo磷酸化的想法一致。这些结果表明,一个家庭的Ste 20激酶可以激活另一个和确定Tao-1作为一个组成部分的调控网络控制HSW途径的信号传导,因此组织生长,在发展过程中。
Recent studies have shown that the Hippo-Salvador-Warts (HSW) pathway restrains tissue growth by phosphorylating and inactivating the oncoprotein Yorkie. How growth suppressive signals are transduced upstream of Hippo remains unclear. We show that the Sterile 20 family kinase, Tao-1, directly phosphorylates T195 in the Hippo activation loop and that, like other HSW pathway genes, Tao-1 functions to restrict cell proliferation in developing imaginal epithelia. This relationship appears to be evolutionarily conserved, because mammalian Tao-1 similarly affects MST kinases. In S2 cells Tao-1 mediates the effects of the upstream HSW components Merlin and Expanded, consistent with the idea that Tao-1 functions in tissues to regulate Hippo phosphorylation. These results demonstrate that one family of Ste20 kinases can activate another and identify Tao-1 as a component of the regulatory network controlling HSW pathway signaling, and therefore tissue growth, during development.
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