PAWS1 controls Wnt signalling through association with casein kinase 1α

PAWS1 通过与酪蛋白激酶 1α 结合来控制 Wnt 信号传导

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作者:Polyxeni Bozatzi, Kevin S Dingwell, Kevin Zl Wu, Fay Cooper, Timothy D Cummins, Luke D Hutchinson, Janis Vogt, Nicola T Wood, Thomas J Macartney, Joby Varghese, Robert Gourlay, David G Campbell, James C Smith, Gopal P Sapkota

Abstract

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 Xenopus embryos activates Wnt signalling and causes complete axis duplication. Consistent with these observations in Xenopus, 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 Xenopus embryos.

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