PAWS1 controls Wnt signalling through association with casein kinase 1α
Polyxeni Bozatzi(MRC Protein Phosphorylation and Ubiquitylation Unit), Kevin S. Dingwell(The Francis Crick Institute), Kevin Z. L. Wu(MRC Protein Phosphorylation and Ubiquitylation Unit), Fay Cooper(The Francis Crick Institute), Timothy D. Cummins(MRC Protein Phosphorylation and Ubiquitylation Unit), Luke D. Hutchinson(MRC Protein Phosphorylation and Ubiquitylation Unit), J. Vogt(MRC Protein Phosphorylation and Ubiquitylation Unit), Nicola T. Wood(MRC Protein Phosphorylation and Ubiquitylation Unit), Thomas Macartney(MRC Protein Phosphorylation and Ubiquitylation Unit), Joby Varghese(MRC Protein Phosphorylation and Ubiquitylation Unit), Robert Gourlay(MRC Protein Phosphorylation and Ubiquitylation Unit), David G. Campbell(MRC Protein Phosphorylation and Ubiquitylation Unit), James C. Smith(The Francis Crick Institute), Gopal P. Sapkota(MRC Protein Phosphorylation and Ubiquitylation Unit)
Cited by 64Open Access
Abstract
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.