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XB-ART-40941
Dev Cell December 1, 2009; 17 (6): 788-99.
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Cell cycle control of wnt receptor activation.

Davidson G , Shen J , Huang YL , Su Y , Karaulanov E , Bartscherer K , Hassler C , Stannek P , Boutros M , Niehrs C .


Abstract
Low-density lipoprotein receptor related proteins 5 and 6 (LRP5/6) are transmembrane receptors that initiate Wnt/beta-catenin signaling. Phosphorylation of PPPSP motifs in the LRP6 cytoplasmic domain is crucial for signal transduction. Using a kinome-wide RNAi screen, we show that PPPSP phosphorylation requires the Drosophila Cyclin-dependent kinase (CDK) L63. L63 and its vertebrate homolog PFTK are regulated by the membrane tethered G2/M Cyclin, Cyclin Y, which mediates binding to and phosphorylation of LRP6. As a consequence, LRP6 phosphorylation and Wnt/beta-catenin signaling are under cell cycle control and peak at G2/M phase; knockdown of the mitotic regulator CDC25/string, which results in G2/M arrest, enhances Wnt signaling in a Cyclin Y-dependent manner. In Xenopus embryos, Cyclin Y is required in vivo for LRP6 phosphorylation, maternal Wnt signaling, and Wnt-dependent anteroposterior embryonic patterning. G2/M priming of LRP6 by a Cyclin/CDK complex introduces an unexpected new layer of regulation of Wnt signaling.

PubMed ID: 20059949
Article link: Dev Cell


Species referenced: Xenopus laevis
Genes referenced: ccny ccnyl1 cdc25b cdc25c foxg1 lrp5 lrp6 odc1 otx2 rasgrf1
Morpholinos: ccny MO1 ccnyl1 MO1 cdc25b MO1 lrp6 MO1


Article Images: [+] show captions
References :
Kaldis, Wnt signaling in mitosis. 2010, Pubmed