Casein kinase 2 associates with and phosphorylates dishevelled.
The dishevelled (dsh) gene of Drosophila melanogaster encodes a phosphoprotein whose phosphorylation state is elevated by Wingless stimulation, suggesting that the phosphorylation of Dsh and the kinase(s) responsible for this phosphorylation are integral parts of the Wg signaling pathway. We found that immunoprecipitated Dsh protein from embryos and from cells in tissue culture is associated with a kinase activity that phosphorylates Dsh in vitro. Purification and peptide sequencing of a 38 kDa protein co-purifying with this kinase activity showed it to be identical to Drosophila Casein Kinase 2 (CK2). Tryptic phosphopeptide mapping indicates that identical peptides are phosphorylated by CK2 in vitro and in vivo, suggesting that CK2 is at least one of the kinases that phosphorylates Dsh. Overexpression of Dfz2, a Wingless receptor, also stimulated phosphorylation of Dsh, Dsh-associated kinase activity, and association of CK2 with Dsh, thus suggesting a role for CK2 in the transduction of the Wg signal.
Willert
K
K
Howard Hughes Medical Institute and Department of Developmental Biology, Stanford University School of Medicine, CA 94305, USA.
Brink
M
M
Wodarz
A
A
Varmus
H
H
Nusse
R
R
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D047390:Casein Kinase II; D002478:Cells, Cultured; D000072261:Dishevelled Proteins; D004330:Drosophila / Q000196:embryology; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D019476:Insect Proteins / Q000378:metabolism*; D010449:Peptide Mapping; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins / Q000096:biosynthesis; D051155:Wnt1 Protein
D048868:Adaptor Proteins, Signal Transducing; D000072261:Dishevelled Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D019476:Insect Proteins; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D017981:Receptors, Neurotransmitter; D011994:Recombinant Proteins; D051155:Wnt1 Protein; C000606588:dsh protein, Drosophila; C101703:fz2 protein, Drosophila; C074622:wg protein, Drosophila; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases