All Dact (Dapper/Frodo) scaffold proteins dimerize and exhibit conserved interactions with Vangl, Dvl, and serine/threonine kinases.
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.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.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.
Mesh Terms:
Adaptor Proteins, Signal Transducing, Animals, Carrier Proteins, Casein Kinase Idelta, Casein Kinase Iepsilon, Catenins, Cell Line, Dimerization, Electrophoresis, Polyacrylamide Gel, Glycogen Synthase Kinase 3, Hepatocyte Nuclear Factor 1-alpha, Histone Deacetylase 1, Humans, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Mice, Molecular Weight, Nerve Tissue Proteins, Phosphoproteins, Protein Interaction Maps, Protein-Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Recombinant Proteins, T Cell Transcription Factor 1
Adaptor Proteins, Signal Transducing, Animals, Carrier Proteins, Casein Kinase Idelta, Casein Kinase Iepsilon, Catenins, Cell Line, Dimerization, Electrophoresis, Polyacrylamide Gel, Glycogen Synthase Kinase 3, Hepatocyte Nuclear Factor 1-alpha, Histone Deacetylase 1, Humans, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Membrane Proteins, Mice, Molecular Weight, Nerve Tissue Proteins, Phosphoproteins, Protein Interaction Maps, Protein-Serine-Threonine Kinases, Receptors, Transforming Growth Factor beta, Recombinant Proteins, T Cell Transcription Factor 1
BMC Biochem.
Date: Jul. 02, 2011
PubMed ID: 21718540
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