Transmembrane protein 198 promotes LRP6 phosphorylation and Wnt signaling activation

Juan Liang, Yu Fu, Cristina Maria Cruciat, Shunji Jia, Ying Wang, Zhen Tong, Qinghua Tao, Dierk Ingelfinger, Michael Boutros, Anming Meng, Christof Niehrs Wu

    Research output: Contribution to journalArticle

    28 Scopus citations

    Abstract

    Wnt/β-catenin signaling is fundamental in embryogenesis and tissue homeostasis in metazoans. Upon Wnt stimulation, cognate coreceptors LRP5 and LRP6 ([LRP5/6] low-density lipoprotein receptor-related proteins 5 and 6) are activated via phosphorylation at key residues. Although several kinases have been implicated, the LRP5/6 activation mechanism remains unclear. Here, we report that transmembrane protein 198 (TMEM198), a previously uncharacterized seven-transmembrane protein, is able to specifically activate LRP6 in transducing Wnt signaling. TMEM198 associates with LRP6 and recruits casein kinase family proteins, via the cytoplasmic domain, to phosphorylate key residues important for LRP6 activation. In mammalian cells, TMEM198 is required for Wnt signaling and casein kinase 1-induced LRP6 phosphorylation. During Xenopus embryogenesis, maternal and zygotic tmem198 mRNAs are widely distributed in the ectoderm and mesoderm. TMEM198 is required for Wnt-mediated neural crest formation, antero-posterior patterning, and particularly engrailed-2 expression in Xenopus embryos. Thus, our results identified TMEM198 as a membrane scaffold protein that promotes LRP6 phosphorylation and Wnt signaling activation.

    Original languageEnglish (US)
    Pages (from-to)2577-2590
    Number of pages14
    JournalMolecular and cellular biology
    Volume31
    Issue number13
    DOIs
    StatePublished - Jul 1 2011

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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  • Cite this

    Liang, J., Fu, Y., Cruciat, C. M., Jia, S., Wang, Y., Tong, Z., Tao, Q., Ingelfinger, D., Boutros, M., Meng, A., & Wu, C. N. (2011). Transmembrane protein 198 promotes LRP6 phosphorylation and Wnt signaling activation. Molecular and cellular biology, 31(13), 2577-2590. https://doi.org/10.1128/MCB.05103-11