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

• DOI: 10.1128/mcb.00550-10
• Publication Date: 2010-10-26T04:00:33Z
• Authors: Igor Červenka; Joshua Wolf; Jan Mašek; Pavel Krejci; William R. Wilcox; Alois Kozubík; Gunnar Schulte; J. Silvio Gutkind; Vítězslav Bryja
• Keywords: LRP6

LDL-related protein 6 (LRP6) is a coreceptor of WNTs and key regulator the WNT/␤-catenin pathway.Upon activation, LRP6 phosphorylated within its intracellular PPPS/TP motifs.These motifs are required to recruit axin inhibit glycogen synthase kinase 3 (GSK3), two basic components ␤-catenin destruction complex.On basis kinome-wide small interfering RNA (siRNA) screen confirmative biochemical analysis, we show that several proline-directed mitogen-activated kinases (MAPKs), such as p38, ERK1/2, JNK1 sufficient for phosphorylation LRP6.External stimuli, which control activity MAPKs, phorbol esters fibroblast growth factor 2 (FGF2) choice LRP6-PPPS/TP regulate amplitude WNT/␤-catenin-dependent transcription.Our findings suggest cells not only one dedicated but rather select their depending on cell type external stimulus.Moreover, direct by MAPKs provides unique point convergence between signaling mitogenic pathways.