PAWS1 controls Wnt signalling through association with casein kinase 1

被引:27
作者
Bozatzi, Polyxeni [1 ]
Dingwell, Kevin S. [2 ]
Wu, Kevin Z. L. [1 ]
Cooper, Fay [2 ]
Cummins, Timothy D. [1 ]
Hutchinson, Luke D. [1 ]
Vogt, Janis [1 ]
Wood, Nicola T. [1 ]
Macartney, Thomas J. [1 ]
Varghese, Joby [1 ]
Gourlay, Robert [1 ]
Campbell, David G. [1 ]
Smith, James C. [2 ]
Sapkota, Gopal P. [1 ]
机构
[1] MRC, Prot Phosphorylat & Ubiquitylat Unit, Dundee, Scotland
[2] Francis Crick Inst, London, England
基金
英国医学研究理事会; 英国惠康基金;
关键词
BMP; CK1; FAM83G; PAWS1; Wnt; BETA-CATENIN; I-EPSILON; PHOSPHORYLATION; PROTEIN; AXIN; INDUCTION; SIAMOIS; PATHWAY; BINDING; COMPLEX;
D O I
10.15252/embr.201744807
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 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.
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页数:18
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