Disease relevance of dsh

• Up-regulation and overproduction of DVL-1, the human counterpart of the Drosophila dishevelled gene, in cervical squamous cell carcinoma [1].

High impact information on dsh

• Finally, accumulation of Dishevelled and Inturned near the basal apparatus of cilia suggests that these proteins function in a common pathway with core PCP components to regulate ciliogenesis [2].
• Planar cell polarity signaling in Drosophila requires the receptor Frizzled and the cytoplasmic proteins Dishevelled and Prickle [3].
• Rescue analysis reveals different protein domain requirements in Dishevelled for the two pathways; the C-terminal DEP domain is essential to rescue planar polarity defects and induce JNK signaling [4].
• Here we show that the transmembrane receptor Notch is required downstream of dsh in R3/R4 for them to adopt distinct fates [5].
• dishevelled and armadillo act in the wingless signalling pathway in Drosophila [6].

Biological context of dsh

• We conclude that dsh, a highly conserved gene, is not merely a permissive factor in Wg signaling but encodes a novel signal transduction molecule, which may function between the Wg receptor and more downstream signaling molecules [7].
• Differential recruitment of Dishevelled provides signaling specificity in the planar cell polarity and Wingless signaling pathways [8].
• Sharp borders of gene expression correlating precisely with clone boundaries suggest that the effects of DSH and SGG on transcription of wg and dpp are not mediated by secreted factors but rather act through intracellular effectors [9].
• While no functional motifs were identified, one region of Dvl-1 was found to be similar to a domain of discs large-1 (dlg), a Drosophila tumor suppressor gene [10].
• Throughout postnatal development of the brain Dvl-1 is highly expressed in areas of high neuronal cell density [10].

Anatomical context of dsh

• A role of Dishevelled in relocating Axin to the plasma membrane during wingless signaling [11].
• Dsh overexpression led to accumulation of Arm primarily in the cytosol and elevation of DE-cadherin at cell junctions [12].
• In the embryo, Dvl-1 is expressed in most tissues, with uniformly high levels in the central nervous system [10].
• Expression of Dvl-1 in adult mice was found to be widespread, with brain and testis exhibiting the highest levels [10].
• This increased signaling correlates with greater colocalized Wg, Arrow, and Dishevelled on endosomes [13].

Associations of dsh with chemical compounds

• Addition of the chelating agent EDTA abolished the in vitro Nkd-Dsh interaction [14].

Physical interactions of dsh

• Yeast two hybrid and in vitro experiments indicate that Nkd directly binds to the basic-PDZ region of Dsh [15].

Co-localisations of dsh

• A portion of Dsh colocalized with Fmi, and the distributions of both proteins were interdependent [16].

Regulatory relationships of dsh

• Overexpression of CKIalpha induced hyper-phosphorylation of both Arm and Dishevelled in S2R+ cells and, conversely, CKIalpha-RNAi reduced the amount of hyper-modified forms [17].

Other interactions of dsh

• The dishevelled protein is modified by wingless signaling in Drosophila [7].
• Dishevelled is a component of the frizzled signaling pathway in Drosophila [18].
• Shaggy and dishevelled exert opposite effects on Wingless and Decapentaplegic expression and on positional identity in imaginal discs [9].
• Specially timed Nkd overexpression is capable of abolishing Dsh function in a distinct signaling pathway that controls planar-cell polarity [15].
• Epistatic genetic studies indicate that Tws functions downstream of Dishevelled and upstream of Sgg and Armadillo [19].

Analytical, diagnostic and therapeutic context of dsh

• EFX corresponds to a minimal domain required for fly or vertebrate Nkd to interact with the basic/PDZ domains of fly Dsh or vertebrate Dvl proteins in the yeast two-hybrid assay [20].
• To learn more about how Dsh can discriminate between these functions, we performed genetic screens to isolate additional dsh alleles and we examined the potential role of protein phosphorylation by site-directed mutagenesis [21].
• Utilizing RT-PCR with degenerate primers, we isolated another member of the mouse Dishevelled (Dvl) gene family, Dvl3 [22].

References