PAWS1 controls Wnt signalling through association with casein kinase 1α

Polyxeni Bozatzi, Kevin S. Dingwell, Kevin Z. L. 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 (Lead / Corresponding author), Gopal P. Sapkota (Lead / Corresponding author)

Research output: Contribution to journalArticle

12 Citations (Scopus)
170 Downloads (Pure)

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.

Original languageEnglish
Article numbere44807
Pages (from-to)1-18
Number of pages18
JournalEMBO Reports
Volume19
Issue number4
Early online date7 Mar 2018
DOIs
Publication statusPublished - 1 Apr 2018

Keywords

  • BMP
  • CK1
  • FAM83G
  • PAWS1
  • Wnt

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  • Student Theses

    Elucidating the biological function of the uncharacterised protein FAM83G/PAWS1: Role in Wnt signalling through its interaction with Caseine Kinase 1α

    Author: Bozatzi, P., 2018

    Supervisor: Sapkota, G. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    File

    Identification of novel protein kinase regulators of TGFβ signalling

    Author: Hutchinson, L., 2019

    Supervisor: Sapkota, G. (Supervisor)

    Student thesis: Doctoral ThesisDoctor of Philosophy

    File

    Profiles

    No photo of Gopal Sapkota

    Sapkota, Gopal

    • MRC PPU - Scientific Programme Leader (MRC)

    Person: Research

    Cite this

    Bozatzi, P., Dingwell, K. S., Wu, K. Z. L., Cooper, F., Cummins, T. D., Hutchinson, L. D., Vogt, J., Wood, N. T., Macartney, T. J., Varghese, J., Gourlay, R., Campbell, D. G., Smith, J. C., & Sapkota, G. P. (2018). PAWS1 controls Wnt signalling through association with casein kinase 1α. EMBO Reports, 19(4), 1-18. [e44807]. https://doi.org/10.15252/embr.201744807