Interplay of signal mediators of decapentaplegic (Dpp): molecular characterization of mothers against dpp, Medea, and daughters against dpp.
Decapentaplegic (Dpp) plays an essential role in Drosophila development, and analyses of the Dpp signaling pathway have contributed greatly to understanding of the actions of the TGF-beta superfamily. Intracellular signaling of the TGF-beta superfamily is mediated by Smad proteins, which are now grouped into three classes. Two Smads have been identified in Drosophila. Mothers against dpp (Mad) is a pathway-specific Smad, whereas Daughters against dpp (Dad) is an inhibitory Smad genetically shown to antagonize Dpp signaling. Here we report the identification of a common mediator Smad in Drosophila, which is closely related to human Smad4. Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. Dad stably associates with Tkv and thereby inhibits Tkv-induced Mad phosphorylation. Dad also blocks hetero-oligomerization and nuclear translocation of Mad. We also show that Mad exists as a monomer in the absence of Tkv stimulation. Tkv induces homo-oligomerization of Mad, and Dad inhibits this step. Finally, we propose a model for Dpp signaling by Drosophila Smad proteins.
Inoue
H
H
Department of Biochemistry, The Cancer Institute, Japanese Foundation for Cancer Research, and Research for the Future Program, Japan Society for the Promotion of Science, Tokyo 170-8455, Japan.
Imamura
T
T
Ishidou
Y
Y
Takase
M
M
Udagawa
Y
Y
Oka
Y
Y
Tsuneizumi
K
K
Tabata
T
T
Miyazono
K
K
Kawabata
M
M
D000595:Amino Acid Sequence; D000818:Animals; D029681:Arabidopsis Proteins; D019556:COS Cells; D002467:Cell Nucleus / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D004330:Drosophila / Q000235:genetics / Q000502:physiology*; D029721:Drosophila Proteins; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry / Q000502:physiology*; D007814:Larva; D008954:Models, Biological; D008969:Molecular Sequence Data; D010940:Plant Proteins / Q000737:chemistry / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051901:Smad4 Protein; D015534:Trans-Activators / Q000737:chemistry / Q000502:physiology; D014157:Transcription Factors; D014162:Transfection
D029681:Arabidopsis Proteins; D004268:DNA-Binding Proteins; C108633:Dad protein, Drosophila; D029721:Drosophila Proteins; D019476:Insect Proteins; C112506:MAD protein, Drosophila; C111712:MEA protein, Arabidopsis; D010940:Plant Proteins; D011994:Recombinant Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D014157:Transcription Factors; C064196:dpp protein, Drosophila