Reference Report

Reference
Citation	Yanfeng, W.A., Berhane, H., Mola, M., Singh, J., Jenny, A., Mlodzik, M. (2011). Functional dissection of phosphorylation of Disheveled in Drosophila. Dev. Biol. 360(1): 132--142. (Export to RIS)
FlyBase ID	FBrf0216602
Publication Type	Research paper
PubMed ID	21963539
PubMed 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 - Dsh(Y473F) behaves like a PCP-specific allele; and (3) defects associated with the PCP specific dsh(1) allele, Dsh(K417M), 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.
DOI	10.1016/j.ydbio.2011.09.017
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Language of Publication	English
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Publication Type	Journal
Abbreviation	Dev. Biol.
Title	Developmental Biology
Publication Year	1959-
ISBN/ISSN	0012-1606
Data from Reference
Alleles (36)
	Abl² dsh^{1.T:Avic\GFP-EGFP} dsh¹ dsh³ dsh^{C-term1-2.T:Avic\GFP-EGFP} dsh^{C-term1-3.T:Avic\GFP-EGFP} dsh^{C-term2-3.T:Avic\GFP-EGFP} dsh^{C-term2.T:Avic\GFP-EGFP} dsh^{C-term5Y-F.T:Avic\GFP-EGFP} dsh^{DEP6A.T:Avic\GFP-EGFP} dsh^{K417R.T:Avic\GFP-EGFP} dsh^{S254A.T:Avic\GFP-EGFP} dsh^{S266A.T:Avic\GFP-EGFP} dsh^{S271A.T:Avic\GFP-EGFP} dsh^{S283A.T:Avic\GFP-EGFP} dsh^{S406A.T:Avic\GFP-EGFP} dsh^{S406E.T:Avic\GFP-EGFP} dsh^{S451A.T:Avic\GFP-EGFP} dsh^{S451E.T:Avic\GFP-EGFP} dsh^{S469A.T:Avic\GFP-EGFP} dsh^{T36A.T:Avic\GFP-EGFP} dsh^{T252A.T:Avic\GFP-EGFP} dsh^{T314A.T:Avic\GFP-EGFP} dsh^{T349A.T:Avic\GFP-EGFP} dsh^{T419A.T:Avic\GFP-EGFP} dsh^{T419E.T:Avic\GFP-EGFP} dsh^{T462A.T:Avic\GFP-EGFP} dsh^{T467A.T:Avic\GFP-EGFP} dsh^{T:Avic\GFP-EGFP} dsh^T:Zzzz\FLAG dsh^{Y24F.T:Avic\GFP-EGFP} dsh^{Y280F.T:Avic\GFP-EGFP} dsh^{Y473F.T:Avic\GFP-EGFP} dsh^{Y474F.T:Avic\GFP-EGFP} dsh^{ΔC.T:Avic\GFP-EGFP} T:Avic\GFP^EGFP
Constructs (32)
	P{dsh.EGFP} P{dsh¹.EGFP} P{dsh-eGFP.C-term1-2} P{dsh-eGFP.C-term1-3} P{dsh-eGFP.C-term2-3} P{dsh-eGFP.C-term2} P{dsh-eGFP.C-term5Y-F} P{dsh-eGFP.DEP6A} P{dsh-eGFP.K417R} P{dsh-eGFP.S254A} P{dsh-eGFP.S266A} P{dsh-eGFP.S271A} P{dsh-eGFP.S283A} P{dsh-eGFP.S406A} P{dsh-eGFP.S406E} P{dsh-eGFP.S451A} P{dsh-eGFP.S451E} P{dsh-eGFP.S469A} P{dsh-eGFP.T36A} P{dsh-eGFP.T252A} P{dsh-eGFP.T314A} P{dsh-eGFP.T349A} P{dsh-eGFP.T419A} P{dsh-eGFP.T419E} P{dsh-eGFP.T462A} P{dsh-eGFP.T467A} P{dsh-eGFP.Y24F} P{dsh-eGFP.Y280F} P{dsh-eGFP.Y473F} P{dsh-eGFP.Y474F} P{dsh-eGFP.ΔC} P{dsh-FLAG}
Genes (8)
	Abl Dll dsh fz fz2 sens stan T:Zzzz\FLAG
Natural transposons (1)
	P-element