Functional dissection of phosphorylation of Disheveled in Drosophila

Wang A. Yanfeng, Hebist Berhane, Marion Mola, Jaskirat Singh, Andreas Jenny, Marek Mlodzik

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

Disheveled/Dsh proteins (Dvl in mammals) are core components of both Wnt/Wg-signaling pathways: canonical β-catenin signaling and Frizzled (Fz)-planar cell polarity (PCP) signaling. Although Dsh is a key cytoplasmic component of both Wnt/Fz-pathways, regulation of its signaling specificity is not well understood. Dsh is phosphorylated, but the functional significance of its phosphorylation remains unclear. We have systematically investigated the phosphorylation of Dsh by combining mass-spectrometry analyses, biochemical studies, and in vivo genetic methods in Drosophila. Our approaches identified multiple phospho-residues of Dsh in vivo. Our data define three novel and unexpected conclusions: (1) strikingly and in contrast to common assumptions, all conserved serines/threonines are non-essential for Dsh function in either pathway; (2) phosphorylation of conserved Tyrosine473 in the DEP domain is critical for PCP-signaling - DshY473F behaves like a PCP-specific allele; and (3) defects associated with the PCP specific dsh1 allele, DshK417M, located within a putative Protein Kinase C consensus site, are likely due to a post-translational modification requirement of Lys417, rather than phosphorylation nearby. In summary, our combined data indicate that while many Ser/Thr and Tyr residues are indeed phosphorylated in vivo, strikingly most of these phosphorylation events are not critical for Dsh function with the exception of DshY473.

Original languageEnglish (US)
Pages (from-to)132-142
Number of pages11
JournalDevelopmental Biology
Volume360
Issue number1
DOIs
StatePublished - Dec 1 2011

Keywords

  • Disheveled
  • PCP
  • Phospho-protein
  • Signaling specificity
  • Wingless
  • Wnt-signaling

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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