Mitogen-Activated Protein Kinases Promote WNT/beta-Catenin Signaling via Phosphorylation of LRP6

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Authors

ČERVENKA Igor WOLF Joshua MAŠEK Jan KREJČÍ Pavel WILCOX William R KOZUBÍK Alois SCHULTE Gunnar GUTKIND J Silvio BRYJA Vítězslav

Year of publication 2011
Type Article in Periodical
Magazine / Source January 2011
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.1128/MCB.00550-10
Field Physiology
Keywords MAPK; mitogen kinases; beta-catenin; wnt; LRP6
Description LDL-related protein 6 (LRP6) is a coreceptor of WNTs and a key regulator of the WNT/beta-catenin pathway. Upon activation LRP6 is phosphorylated within its intracellular PPPS/TP motifs. On the basis of a kinome-wide siRNA screen and confirmative biochemical analysis, we show that several proline-directed mitogen-activated protein kinases (MAPKs), such as p38, ERK1/2 and JNK1 are sufficient and required for the phosphorylation of PPPS/TP motifs of LRP6. External stimuli, which control the activity of MAPKs, such as phorbolesters and fibroblast growth factor 2 (FGF2) control the choice of the LRP6-PPPS/TP kinase and regulate the amplitude of LRP6 phosphorylation and WNT/beta-catenin-dependent transcription. Our findings suggest that cells recruit not only one dedicated LRP6 kinase but rather select their LRP6 kinase depending on cell type and the external stimulus.
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