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Mol Cell Biol 2011 Jul 01;3113:2577-90. doi: 10.1128/MCB.05103-11.
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Transmembrane protein 198 promotes LRP6 phosphorylation and Wnt signaling activation.

Liang J , Fu Y , Cruciat CM , Jia S , Wang Y , Tong Z , Tao Q , Ingelfinger D , Boutros M , Meng A , Niehrs C , Wu W .

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.

PubMed ID: 21536646
PMC ID: PMC3133378
Article link: Mol Cell Biol

Species referenced: Xenopus
Genes referenced: ctnnb1 en2 lrp5 lrp6 tmem198
GO keywords: Wnt signaling pathway
Morpholinos: tmem198 MO1 tmem198 MO2

References [+] :
Angers, Proximal events in Wnt signal transduction. 2009, Pubmed