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PAWS1 controls Wnt signalling through association with casein kinase 1α
Authors: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
Institution:1. Medical Research Council Protein Phosphorylation and Ubiquitylation Unit, Dundee, UK;2. The Francis Crick Institute, London, UK
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.
Keywords:   BMP     CK1  FAM83G  PAWS1  Wnt
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