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Regulation of Lrp6 phosphorylation

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Abstract

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.

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Acknowledgments

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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Authors and Affiliations

  1. Division of Molecular Embryology, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany

    Christof Niehrs

  2. Division of Molecular Biology of the Cell I, DKFZ-ZMBH Alliance, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany

    Jinlong Shen

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  1. Christof Niehrs
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Correspondence to Christof Niehrs.

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Niehrs, C., Shen, J. Regulation of Lrp6 phosphorylation. Cell. Mol. Life Sci. 67, 2551–2562 (2010). https://doi.org/10.1007/s00018-010-0329-3

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  • DOI: https://doi.org/10.1007/s00018-010-0329-3

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