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EMBO Rep 2018 Apr 01;194:. doi: 10.15252/embr.201744807.
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PAWS1 controls Wnt signalling through association with casein kinase 1α.

Bozatzi P , Dingwell KS , Wu KZ , Cooper F , Cummins TD , Hutchinson LD , Vogt J , Wood NT , Macartney TJ , Varghese J , Gourlay R , Campbell DG , Smith JC , Sapkota GP .

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.

PubMed ID: 29514862
PMC ID: PMC5891436
Article link: EMBO Rep
Grant support: [+]

Species referenced: Xenopus
Genes referenced: axin1 bmp2 bmp4 chrd csnk1a1 ctnnb1 egfr fam83g gsk3b isyna1 lrp6 msx1 nfatc2 per2 prss1 sia1 smad1 ventx2 ventx2.2 vim wnt3a wnt8a
GO keywords: axis specification [+]
Antibodies: Csnk1A1 Ab1 Ctnnb1 Ab15 Ctnnb1 Ab2 Gapdh Ab4 Tuba4a Ab3

Article Images: [+] show captions
References [+] :
Amit, Axin-mediated CKI phosphorylation of beta-catenin at Ser 45: a molecular switch for the Wnt pathway. 2002, Pubmed