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@article{1094503, author = {Červenka, Igor and Wolf, Joshua and Mašek, Jan and Krejčí, Pavel and Wilcox, William R. and Kozubík, Alois and Schulte, Gunnar and Gutkind, Silvio J. and Bryja, Vítězslav}, article_number = {1}, doi = {http://dx.doi.org/10.1128/MCB.00550-10}, keywords = {Wnt; beta-catenin; LRP6; MAPKs}, language = {eng}, issn = {0270-7306}, journal = {Molecular and cellular biology}, title = {Mitogen-Activated Protein Kinases Promote WNT/beta-Catenin Signaling via Phosphorylation of LRP6}, volume = {31}, year = {2011} }
TY - JOUR ID - 1094503 AU - Červenka, Igor - Wolf, Joshua - Mašek, Jan - Krejčí, Pavel - Wilcox, William R. - Kozubík, Alois - Schulte, Gunnar - Gutkind, Silvio J. - Bryja, Vítězslav PY - 2011 TI - Mitogen-Activated Protein Kinases Promote WNT/beta-Catenin Signaling via Phosphorylation of LRP6 JF - Molecular and cellular biology VL - 31 IS - 1 SP - 179-189 EP - 179-189 SN - 02707306 KW - Wnt KW - beta-catenin KW - LRP6 KW - MAPKs N2 - 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. These phosphorylated motifs are required to recruit axin and to inhibit glycogen synthase kinase 3 (GSK3), two basic components of the beta-catenin destruction complex. On the basis of a kinome-wide small interfering RNA (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 phorbol esters 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 not only recruit one dedicated LRP6 kinase but rather select their LRP6 kinase depending on cell type and the external stimulus. Moreover, direct phosphorylation of LRP6 by MAPKs provides a unique point for convergence between WNT/beta-catenin signaling and mitogenic pathways. ER -
ČERVENKA, Igor, Joshua WOLF, Jan MAŠEK, Pavel KREJČÍ, William R. WILCOX, Alois KOZUBÍK, Gunnar SCHULTE, Silvio J. GUTKIND a Vítězslav BRYJA. Mitogen-Activated Protein Kinases Promote WNT/beta-Catenin Signaling via Phosphorylation of LRP6. \textit{Molecular and cellular biology}. roč.~31, č.~1, s.~179-189. ISSN~0270-7306. doi:10.1128/MCB.00550-10. 2011.
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