title: All Dact (Dapper/Frodo) scaffold proteins dimerize and exhibit conserved interactions with Vangl, Dvl, and serine/threonine kinases.
abstract: BACKGROUND
  The Dact family of scaffold proteins was discovered by virtue of binding to Dvl proteins central to Wnt and Planar Cell Polarity (PCP) signaling. Subsequently Dact proteins have been linked to a growing list of potential partners implicated in β-catenin-dependent and β-catenin-independent forms of Wnt and other signaling. To clarify conserved and non-conserved roles for this protein family, we systematically compared molecular interactions of all three murine Dact paralogs by co-immunoprecipitation of proteins recombinantly expressed in cultured human embryonic kidney cells.
  
  
  RESULTS
  Every Dact paralog readily formed complexes with the Vangl, Dvl, and CK1δ/ε proteins of species ranging from fruit flies to humans, as well as with PKA and PKC. Dact proteins also formed complexes with themselves and with each other; their conserved N-terminal leucine-zipper domains, which have no known binding partners, were necessary and sufficient for this interaction, suggesting that it reflects leucine-zipper-mediated homo- and hetero-dimerization. We also found weaker, though conserved, interactions of all three Dact paralogs with the catenin superfamily member p120ctn. Complex formation with other previously proposed partners including most other catenins, GSK3, LEF/TCF, HDAC1, and TGFβ receptors was paralog-specific, comparatively weak, and/or more sensitive to empirical conditions.
  
  
  CONCLUSIONS
  Combined with published functional evidence from targeted knock-out mice, these data support a conserved role for Dact proteins in kinase-regulated biochemistry involving Vangl and Dvl. This strongly suggests that a principal role for all Dact family members is in the PCP pathway or a molecularly related signaling cascade in vertebrates.
authors: The Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California San Francisco, 1550 4th St, San Francisco CA 94158-2324, USA. bc@ucsf.edu
authors: Saul
authors: S
authors: Kivimäe
authors: Xiao Yong
authors: XY
authors: Yang
authors: Benjamin N R
authors: BN
authors: Cheyette
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D048149:Casein Kinase 1 epsilon / Q000378:metabolism; D048148:Casein Kinase Idelta / Q000378:metabolism; D051177:Catenins / Q000378:metabolism; D002460:Cell Line; D019281:Dimerization; D000072261:Dishevelled Proteins; D004591:Electrophoresis, Polyacrylamide Gel; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000378:metabolism; D056284:Histone Deacetylase 1 / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D060066:Protein Interaction Maps; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016601:RNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D051822:T Cell Transcription Factor 1 / Q000378:metabolism; D000095002:Delta Catenin
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D051177:Catenins; C514734:Dact2 protein, mouse; C514671:Dact3 protein, mouse; D000072261:Dishevelled Proteins; C496487:HNF1A protein, human; D051538:Hepatocyte Nuclear Factor 1-alpha; D047908:Intracellular Signaling Peptides and Proteins; C431577:Ltap protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; D051822:T Cell Transcription Factor 1; C497576:TCF7 protein, human; C528120:Vangl1 protein, mouse; C508545:frodo protein, mouse; D048149:Casein Kinase 1 epsilon; D048148:Casein Kinase Idelta; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1; D000095002:Delta Catenin