Human dishevelled genes constitute a DHR-containing multigene family.

Three human genes encoding proteins homologous to Drosophila Dishevelled protein were cloned and characterized. Amino acid similarity between the different Dishevelled proteins is concentrated in three highly conserved regions. Two of these regions do not exhibit significant sequence similarity with other known proteins; the third is similar to the discs-large homology region, which was first found in a Drosophila Discs-large tumor suppressor protein (also known as GLGF or PDZ domain). We produced antibodies against human Dishevelled-2 and demonstrated that it is a phosphoprotein and can be detected in all cell lines and human embryonic tissues examined. Indirect immunofluorescence indicates that it is found throughout the cytoplasm. Our results indicate that the human dishevelled genes constitute a multigene family and that Dishevelled proteins are highly conserved among metazoans.

[1]  D. Beier,et al.  Isolation and characterization of mouse Dishevelled‐3 , 1996, Developmental dynamics : an official publication of the American Association of Anatomists.

[2]  R. Moon,et al.  A frizzled homolog functions in a vertebrate Wnt signaling pathway , 1996, Current Biology.

[3]  N. Perrimon,et al.  Conservation of dishevelled structure and function between flies and mice: isolation and characterization of Dvl2 , 1996, Mechanisms of Development.

[4]  Jeremy Nathans,et al.  A new member of the frizzled family from Drosophila functions as a Wingless receptor , 1996, Nature.

[5]  John H. Lewis,et al.  Crystal Structures of a Complexed and Peptide-Free Membrane Protein–Binding Domain: Molecular Basis of Peptide Recognition by PDZ , 1996, Cell.

[6]  B. Dallapiccola,et al.  Human homologue sequences to the Drosophila dishevelled segment-polarity gene are deleted in the DiGeorge syndrome. , 1996, American journal of human genetics.

[7]  N. Perrimon,et al.  Interaction Between Wingless and Notch Signaling Pathways Mediated by Dishevelled , 1996, Science.

[8]  D. Bredt,et al.  Interaction of Nitric Oxide Synthase with the Postsynaptic Density Protein PSD-95 and α1-Syntrophin Mediated by PDZ Domains , 1996, Cell.

[9]  J. Nathans,et al.  A Large Family of Putative Transmembrane Receptors Homologous to the Product of the Drosophila Tissue Polarity Gene frizzled(*) , 1996, The Journal of Biological Chemistry.

[10]  Y. Jan,et al.  Clustering of Shaker-type K+ channels by interaction with a family of membrane-associated guanylate kinases , 1995, Nature.

[11]  P. Seeburg,et al.  Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. , 1995, Science.

[12]  M. Kennedy Origin of PDZ (DHR, GLGF) domains. , 1995, Trends in biochemical sciences.

[13]  N. Perrimon,et al.  Dorsalizing and neuralizing properties of Xdsh, a maternally expressed Xenopus homolog of dishevelled. , 1995, Development.

[14]  J. Klingensmith,et al.  The dishevelled protein is modified by wingless signaling in Drosophila. , 1995, Genes & development.

[15]  Andrew P. McMahon,et al.  Dorsalizing signal Wnt-7a required for normal polarity of D–V and A–P axes of mouse limb , 1995, Nature.

[16]  C P Ponting,et al.  DHR domains in syntrophins, neuronal NO synthases and other intracellular proteins. , 1995, Trends in biochemical sciences.

[17]  A. McMahon,et al.  Epithelial transformation of metanephric mesenchyme in the developing kidney regulated by Wnt-4 , 1994, Nature.

[18]  A. Brown,et al.  Induction of kidney epithelial morphogenesis by cells expressing Wnt-1. , 1994, Developmental biology.

[19]  N. Perrimon,et al.  Isolation and characterization of a mouse homolog of the Drosophila segment polarity gene dishevelled. , 1994, Developmental biology.

[20]  A. M. Arias,et al.  Notch is required for wingless signaling in the epidermis of Drosophila , 1994, Cell.

[21]  T. Dale,et al.  Developmental and hormonal regulation of Wnt gene expression in the mouse mammary gland. , 1994, Differentiation; research in biological diversity.

[22]  A. McMahon,et al.  Wnt genes and vertebrate development. , 1994, Current opinion in genetics & development.

[23]  A. McMahon,et al.  Wnt-3a regulates somite and tailbud formation in the mouse embryo. , 1994, Genes & development.

[24]  R. Durbin,et al.  2.2 Mb of contiguous nucleotide sequence from chromosome III of C. elegans , 1994, Nature.

[25]  H. Theisen,et al.  dishevelled is required during wingless signaling to establish both cell polarity and cell identity. , 1994, Development.

[26]  Norbert Perrimon,et al.  dishevelled and armadillo act in the Wingless signalling pathway in Drosophila , 1994, Nature.

[27]  Norbert Perrimon,et al.  Components of wingless signalling in Drosophila , 1994, Nature.

[28]  P. Bryant,et al.  Tumor suppressor genes encoding proteins required for cell interactions and signal transduction in Drosophila. , 1993, Development (Cambridge, England). Supplement.

[29]  R. Moon In pursuit of the functions of the Wnt family of developmental regulators: Insights from Xenopus laevis , 1993, BioEssays : news and reviews in molecular, cellular and developmental biology.

[30]  P. Ingham,et al.  Cloning and characterization of a novel Drosophila Wnt gene, Dwnt-5, a putative downstream target of the homeobox gene distal-less. , 1992, Developmental biology.

[31]  M. Snyder,et al.  The nuclear-mitotic apparatus protein is important in the establishment and maintenance of the bipolar mitotic spindle apparatus. , 1992, Molecular biology of the cell.

[32]  R. Nusse,et al.  Isolation and expression of two novel Wnt/wingless gene homologues in Drosophila. , 1992, Development.

[33]  A. McMahon,et al.  Differential regulation of the Wnt gene family during pregnancy and lactation suggests a role in postnatal development of the mammary gland , 1992, Molecular and cellular biology.

[34]  R. Steward,et al.  Requirement for phosphorylation and localization of the Bicaudal-D protein in Drosophila oocyte differentiation , 1991, Cell.

[35]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[36]  Andrew P. McMahon,et al.  The Wnt-1 (int-1) proto-oncogene is required for development of a large region of the mouse brain , 1990, Cell.

[37]  Mario R. Capecchi,et al.  Targeted disruption of the murine int-1 proto-oncogene resulting in severe abnormalities in midbrain and cerebellar development , 1990, Nature.

[38]  M. Kozak The scanning model for translation: an update , 1989, The Journal of cell biology.

[39]  H. Varmus,et al.  Expression of the int-1 gene in transgenic mice is associated with mammary gland hyperplasia and adenocarcinomas in male and female mice , 1988, Cell.

[40]  D. Smith,et al.  Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase. , 1988, Gene.

[41]  Detlef Weigel,et al.  The Drosophila homology of the mouse mammary oncogene int-1 is identical to the segment polarity gene wingless , 1987, Cell.

[42]  Y. Graba,et al.  DWnt-4, a novel Drosophila Wnt gene acts downstream of homeotic complex genes in the visceral mesoderm. , 1995, Development.

[43]  N. Perrimon,et al.  The Drosophila segment polarity gene dishevelled encodes a novel protein required for response to the wingless signal. , 1994, Genes & development.

[44]  R. W. Davis,et al.  Lambda gt 11: gene isolation with antibody probes and other applications. , 1987, Methods in enzymology.