Casein kinase 2 associates with and phosphorylates dishevelled

K Willert; M Brink; A Wodarz; H Varmus; R Nusse

doi:10.1093/emboj/16.11.3089

Casein kinase 2 associates with and phosphorylates dishevelled

EMBO J. 1997 Jun 2;16(11):3089-96. doi: 10.1093/emboj/16.11.3089.

Authors

K Willert¹, M Brink, A Wodarz, H Varmus, R Nusse

Affiliation

¹ Howard Hughes Medical Institute and Department of Developmental Biology, Stanford University School of Medicine, CA 94305, USA.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adaptor Proteins, Signal Transducing
Animals
Casein Kinase II
Cells, Cultured
Dishevelled Proteins
Drosophila / embryology
Drosophila Proteins*
Frizzled Receptors
Insect Proteins / metabolism*
Peptide Mapping
Phosphoproteins / metabolism*
Phosphorylation
Protein Binding
Protein Serine-Threonine Kinases / metabolism*
Proto-Oncogene Proteins
Receptors, Cell Surface / biosynthesis
Receptors, Cell Surface / genetics
Receptors, G-Protein-Coupled
Receptors, Neurotransmitter*
Recombinant Proteins / biosynthesis
Wnt1 Protein

Substances

Adaptor Proteins, Signal Transducing
Dishevelled Proteins
Drosophila Proteins
Frizzled Receptors
Insect Proteins
Phosphoproteins
Proto-Oncogene Proteins
Receptors, Cell Surface
Receptors, G-Protein-Coupled
Receptors, Neurotransmitter
Recombinant Proteins
Wnt1 Protein
dsh protein, Drosophila
fz2 protein, Drosophila
wg protein, Drosophila
Casein Kinase II
Protein Serine-Threonine Kinases