Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo
Protein kinase A is a common negative regulator of Hedgehog signaling in the vertebrate embryo
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DOI：
10.1101/gad.10.6.647
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发表时间：
1996-03-15
影响因子：
10.5
通讯作者：
McMahon, AP
中科院分区：
文献类型：
--
作者：
Hammerschmidt, M;Bitgood, MJ;McMahon, AP
刺猬（Hh）家族成员的中线信号与脊椎动物胚胎的模式有关。我们已经探索了camp依赖性蛋白激酶A （PKA）在这些事件中的潜在调节作用。将编码Sonic hedgehog基因（Shh）、Indian hedgehog基因（Ihh）或PKA的显性负调控亚基PKI的rna注入斑马鱼胚胎，具有相同的表型。这些包括眼内近端区扩张，脑内腹侧区扩张，体和头间质内近端区扩张。此外，PKI的异位表达部分修复了缺乏正常合成Shh的中线结构的无尾突变体和独眼突变体的体和视柄缺陷。相反，在胚胎中注入编码PKA组成活性催化亚基（PKA*）的RNA后，hhs和PKI异位表达促进的所有细胞类型都受到抑制。这些结果以及PKA*阻断异位Hh信号传导的上位性研究表明，PKA在靶细胞中作为Hedgehog信号传导的常见负调控因子。
Midline signaling by Hedgehog (Hh) family members has been implicated in patterning the vertebrate embryo. We have explored the potential regulatory role of cAMP-dependent protein kinase A (PKA) in these events. Zebrafish embryos injected with RNAs encoding Sonic hedgehog (Shh), Indian hedgehog (Ihh), or a dominant-negative regulatory subunit of PKA, PKI, have equivalent phenotypes. These include the expansion of proximal fates in the eye, ventral fates in the brain, and adaxial fates in somites and head mesenchyme. Moreover, ectopic expression of PKI partially rescues somite and optic stalk defects in no tail and cyclops mutants that lack midline structures that normally synthesize Shh. Conversely, all cell types promoted by ectopic expression of hhs and PKI are suppressed in embryos injected with RNA encoding a constitutively active catalytic subunit of PKA (PKA*). These results, together with epistasis studies on the block of ectopic Hh signaling by PKA*, indicate that PKA acts in target cells as a common negative regulator of Hedgehog signaling.