Mitogen-Activated Protein Kinases Promote WNT/beta-Catenin Signaling via Phosphorylation of LRP6
| Autoři | |
|---|---|
| Rok publikování | 2011 |
| Druh | Článek v odborném periodiku |
| Časopis / Zdroj | January 2011 |
| Fakulta / Pracoviště MU | |
| Citace | |
| Doi | http://dx.doi.org/10.1128/MCB.00550-10 |
| Obor | Fyziologie |
| Klíčová slova | MAPK; mitogen kinases; beta-catenin; wnt; LRP6 |
| Popis | 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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