PT  - JOURNAL ARTICLE
AU  - S. M. Tsang
AU  - William Cheng
AU  - Jingjing Li
AU  - Jeremy B. A. Green
TI  - PI4K2β constrains non-canonical Wnt-PCP signalling and is localised by PAR-1 (MARK2/3) phosphorylation
AID  - 10.1101/660431
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 660431
4099  - http://biorxiv.org/content/early/2019/06/18/660431.short
4100  - http://biorxiv.org/content/early/2019/06/18/660431.full
AB  - Canonical Wnt signalling is critically important in embryonic cell-type specification and cancer, while non-canonical Wnt signalling is primarily implicated in physical morphogenesis, especially planar cell polarity (PCP). Both are modulated by the polarity kinase PAR-1 (MARK2/3). PAR-1 phosphorylates the Wnt transducer Dishevelled, but there is evidence that it exerts control through other targets. Here we describe an in vitro screen for new targets of PAR-1 in which we identified phosphatidyl-inositol-4-kinase-2-beta (PI4K2β) as a substrate. Perturbation phenotypes and reporter assays in vivo show that PI4K2β inhibits both canonical and non-canonical Wnt pathways, in contrast to PI4K2α, which promotes canonical but does not affect non-canonical signalling. We show that PI4K2β acts in Wnt-responding tissue, not in Wnt production or secretion. Subcellularly, PI4K2β is cortically enriched, unlike PI4K2α, and is basolateral in polarised cells. Mutation of the PAR-1 phosphorylation site of PI4K2β mis-localises it and the endogenous core PCP protein, Vangl2. Our results reveal that PAR-1 interacts with the vertebrate PCP signalling pathway via PI4K2β.