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bioRxiv · 10.1101/660431

PI4K2β constrains non-canonical Wnt-PCP signalling and is localised by PAR-1 (MARK2/3) phosphorylation

Tsang, S. M.·Cheng, W.·Green, J. B. A.·Li, J.
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Abstract

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 (PI4K2{beta}) as a substrate. Perturbation phenotypes and reporter assays in vivo show that PI4K2{beta} inhibits both canonical and non-canonical Wnt pathways, in contrast to PI4K2, which promotes canonical but does not affect non-canonical signalling. We show that PI4K2{beta} acts in Wnt-responding tissue, not in Wnt production or secretion. Subcellularly, PI4K2{beta} is cortically enriched, unlike PI4K2, and is basolateral in polarised cells. Mutation of the PAR-1 phosphorylation site of PI4K2{beta} mis-localises it and the endogenous core PCP protein, Vangl2. Our results reveal that PAR-1 interacts with the vertebrate PCP signalling pathway via PI4K2{beta}.

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Tsang, S. M., Cheng, W., Green, J. B. A., Li, J.. 2019-06-18. PI4K2β constrains non-canonical Wnt-PCP signalling and is localised by PAR-1 (MARK2/3) phosphorylation. https://doi.org/10.1101/660431

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