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Gain-of-function Shh mutants activate Smo cell-autonomously independent of Ptch1/2 function
Mechanisms of Development ( IF 2.6 ) Pub Date : 2018-10-01 , DOI: 10.1016/j.mod.2018.08.009
Catalina Casillas 1 , Henk Roelink 1
Affiliation  

Sonic Hedgehog (Shh) signaling is characterized by non-cell autonomy; cells expressing Shh do not respond to the ligand. Here, we identify several Shh mutations that can activate the Hedgehog (Hh) pathway cell-autonomously. Cell-autonomous pathway activation requires the extracellular cysteine rich domain of Smoothened, but is otherwise independent of the Shh receptors Patched1 and -2. Many of the Shh mutants that gain activity fail to undergo auto processing resulting in the perdurance of the Shh pro-peptide, a form of Shh that is sufficient to activate the Hh response cell-autonomously. Our results demonstrate that Shh is capable of activating the Hh pathway via Smoothened, independently of Patched1/2, and that it harbors an intrinsic mechanism that prevents cell-autonomous activation of the Shh response.

中文翻译:

功能获得性 Shh 突变体独立于 Ptch1/2 功能自主激活 Smo 细胞

Sonic Hedgehog (Shh) 信号的特点是非细胞自主性;表达 Shh 的细胞不响应配体。在这里,我们确定了几个可以自主激活刺猬 (Hh) 通路的 Shh 突变。细胞自主途径激活需要 Smoothened 细胞外富含半胱氨酸的结构域,但在其他方面独立于 Shh 受体 Patched1 和 -2。许多获得活性的 Shh 突变体无法进行自动加工,导致 Shh 前肽的持久性,Shh 的一种形式足以自主激活 Hh 反应细胞。我们的结果表明,Shh 能够通过 Smoothened 激活 Hh 通路,独立于 Patched1/2,并且它具有阻止细胞自主激活 Shh 反应的内在机制。
更新日期:2018-10-01
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