TY - JOUR
T1 - The dishevelled protein is modified by wingless signaling in Drosophila
AU - Yanagawa, S
AU - van Leeuwen, F
AU - Wodarz, A
AU - Klingensmith, J
AU - Nusse, R
PY - 1995/5/1
Y1 - 1995/5/1
N2 - Wingless (Wg) is an important signaling molecule in the development of Drosophila, but little is known about its signal transduction pathway. Genetic evidence indicates that another segment polarity gene, dishevelled (dsh) is required for Wg signaling. We have recently developed a cell culture system for Wg protein activity, and using this in vitro system as well as intact Drosophila embryos, we have analyzed biochemical changes in the Dsh protein as a consequence of Wg signaling. We find that Dsh is a phosphoprotein, normally present in the cytoplasm. Wg signaling generates a hyperphosphorylated form of Dsh, which is associated with a membrane fraction. Overexpressed Dsh becomes hyperphosphorylated in the absence of extracellular Wg and increases levels of the Armadillo protein, thereby mimicking the Wg signal. A deletional analysis of Dsh identifies several conserved domains essential for activity, among which is a so-called GLGF/DHR motif. We conclude that dsh, a highly conserved gene, is not merely a permissive factor in Wg signaling but encodes a novel signal transduction molecule, which may function between the Wg receptor and more downstream signaling molecules.
AB - Wingless (Wg) is an important signaling molecule in the development of Drosophila, but little is known about its signal transduction pathway. Genetic evidence indicates that another segment polarity gene, dishevelled (dsh) is required for Wg signaling. We have recently developed a cell culture system for Wg protein activity, and using this in vitro system as well as intact Drosophila embryos, we have analyzed biochemical changes in the Dsh protein as a consequence of Wg signaling. We find that Dsh is a phosphoprotein, normally present in the cytoplasm. Wg signaling generates a hyperphosphorylated form of Dsh, which is associated with a membrane fraction. Overexpressed Dsh becomes hyperphosphorylated in the absence of extracellular Wg and increases levels of the Armadillo protein, thereby mimicking the Wg signal. A deletional analysis of Dsh identifies several conserved domains essential for activity, among which is a so-called GLGF/DHR motif. We conclude that dsh, a highly conserved gene, is not merely a permissive factor in Wg signaling but encodes a novel signal transduction molecule, which may function between the Wg receptor and more downstream signaling molecules.
KW - Adaptor Proteins, Signal Transducing
KW - Animals
KW - Armadillo Domain Proteins
KW - Base Sequence
KW - Cell Extracts
KW - Cell Membrane/chemistry
KW - Cells, Cultured
KW - Conserved Sequence/genetics
KW - Cytoplasm/chemistry
KW - Dishevelled Proteins
KW - Drosophila/embryology
KW - Drosophila Proteins
KW - Gene Expression Regulation
KW - Gene Expression Regulation, Developmental
KW - Genes, Insect/genetics
KW - Molecular Sequence Data
KW - Molecular Weight
KW - Phosphoproteins/analysis
KW - Protein Biosynthesis
KW - Proteins/analysis
KW - Proto-Oncogene Proteins/physiology
KW - Recombinant Fusion Proteins/biosynthesis
KW - Sequence Deletion/physiology
KW - Signal Transduction/genetics
KW - Trans-Activators
KW - Transcription Factors
KW - Wnt1 Protein
UR - http://www.scopus.com/inward/record.url?scp=0028989112&partnerID=8YFLogxK
U2 - 10.1101/gad.9.9.1087
DO - 10.1101/gad.9.9.1087
M3 - Article
C2 - 7744250
SN - 0890-9369
VL - 9
SP - 1087
EP - 1097
JO - Genes and Development
JF - Genes and Development
IS - 9
ER -