Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Dundee, UK.
The Francis Crick Institute, London, UK.
EMBO Rep. 2018 Apr;19(4). doi: 10.15252/embr.201744807. Epub 2018 Mar 7.
The BMP and Wnt signalling pathways determine axis specification during embryonic development. Our previous work has shown that PAWS1 (also known as FAM83G) interacts with SMAD1 and modulates BMP signalling. Here, surprisingly, we show that overexpression of PAWS1 in embryos activates Wnt signalling and causes complete axis duplication. Consistent with these observations in , Wnt signalling is diminished in U2OS osteosarcoma cells lacking PAWS1, while BMP signalling is unaffected. We show that PAWS1 interacts and co-localises with the α isoform of casein kinase 1 (CK1), and that PAWS1 mutations incapable of binding CK1 fail both to activate Wnt signalling and to elicit axis duplication in embryos.
BMP 和 Wnt 信号通路决定胚胎发育过程中的轴 Specification。我们之前的工作表明，PAWS1（也称为 FAM83G）与 SMAD1 相互作用并调节 BMP 信号。在这里，令人惊讶的是，我们表明在 胚胎中过表达 PAWS1 会激活 Wnt 信号通路并导致完全的轴复制。与这些在 中的观察结果一致，在缺乏 PAWS1 的 U2OS 骨肉瘤细胞中，Wnt 信号通路减少，而 BMP 信号通路不受影响。我们表明 PAWS1 与酪蛋白激酶 1（CK1）的α同工型相互作用并共定位，并且不能与 CK1 结合的 PAWS1 突变既不能激活 Wnt 信号通路，也不能在 胚胎中引发轴复制。
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