Cellular and Molecular Life Sciences

, Volume 67, Issue 15, pp 2551–2562 | Cite as

Regulation of Lrp6 phosphorylation

  • Christof NiehrsEmail author
  • Jinlong Shen


The Wnt/β-catenin signaling pathway plays important roles in embryonic development and tissue homeostasis, and is implicated in human disease. Wnts transduce signals via transmembrane receptors of the Frizzled (Fzd/Fz) family and the low density lipoprotein receptor-related protein 5/6 (Lrp5/6). A key mechanism in their signal transduction is that Wnts induce Lrp6 signalosomes, which become phosphorylated at multiple conserved sites, notably at PPSPXS motifs. Lrp6 phosphorylation is crucial to β-catenin stabilization and pathway activation by promoting Axin and Gsk3 recruitment to phosphorylated sites. Here, we summarize how proline-directed kinases (Gsk3, PKA, Pftk1, Grk5/6) and non-proline-directed kinases (CK1 family) act upon Lrp6, how the phosphorylation is regulated by ligand binding and mitosis, and how Lrp6 phosphorylation leads to β-catenin stabilization.


Wnt Lrp6 Phosphorylation Protein kinase Parathyroid hormone CK1 Gsk3 Ccny Cell cycle 



We apologize to the colleagues in the Wnt field, whose work is not cited due to the limitation of space. We thank M. Bienz for critical reading of the manuscript.


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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  1. 1.Division of Molecular EmbryologyDKFZ-ZMBH Alliance, Deutsches KrebsforschungszentrumHeidelbergGermany
  2. 2.Division of Molecular Biology of the Cell IDKFZ-ZMBH Alliance, Deutsches KrebsforschungszentrumHeidelbergGermany

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