PAWS1 controls Wnt signalling through association with casein kinase 1α

EMBO Rep. 2018 Apr;19(4):e44807. doi: 10.15252/embr.201744807. Epub 2018 Mar 7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Axin Protein / metabolism
  • Bone Morphogenetic Proteins / metabolism
  • Casein Kinase Ialpha / metabolism*
  • Cell Line, Tumor
  • Cell Nucleus
  • Ectopic Gene Expression
  • Gene Expression
  • Gene Knockout Techniques
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Multiprotein Complexes / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Transport
  • Wnt Signaling Pathway*
  • Xenopus
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism
  • beta Catenin / metabolism

Substances

  • AXIN1 protein, human
  • Axin Protein
  • Bone Morphogenetic Proteins
  • FAM83G protein, human
  • Intracellular Signaling Peptides and Proteins
  • Multiprotein Complexes
  • Xenopus Proteins
  • beta Catenin
  • Casein Kinase Ialpha