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PAWS1 controls Wnt signalling through association with casein kinase 1α
journal contributionposted on 2020-07-01, 11:08 authored by 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
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.
BMPCK1FAM83GPAWS1WntAnimalsAxin ProteinBone Morphogenetic ProteinsCasein Kinase IalphaCell Line, TumorCell NucleusEctopic Gene ExpressionGene ExpressionGene Knockout TechniquesHumansIntracellular Signaling Peptides and ProteinsMultiprotein ComplexesPhosphorylationProtein BindingProtein TransportWnt Signaling PathwayXenopusXenopus Proteinsbeta CateninSmith FC001157Developmental Biology0601 Biochemistry and Cell Biology