Abstract
Wishful thinking (Wit) is a Drosophila transforming growth factor-beta (TGFbeta) superfamily type II receptor most related to the mammalian bone morphogenetic protein (BMP) type II receptor, BMPRII. To better understand its function, we undertook a biochemical approach to establish the ligand binding repertoire and downstream signaling pathway. We observed that BMP4 and BMP7, bound to receptor complexes comprised of Wit and the type I receptor thickveins and saxophone to activate a BMP-like signaling pathway. Further we demonstrated that both myoglianin and its most closely related mammalian ligand, myostatin, interacted with a Wit and Baboon (Babo) type II-type I receptor complex to activate TGFbeta/activin-like signaling pathways. These results thereby demonstrate that Wit binds multiple ligands to activate both BMP and TGFbeta-like signaling pathways. Given that myoglianin is expressed in muscle and glial-derived cells, these results also suggest that Wit may mediate myoglianin-dependent signals in the nervous system.
MeSH terms
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Activin Receptors / genetics
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Activin Receptors / metabolism
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Animals
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Bone Morphogenetic Protein Receptors, Type I
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Bone Morphogenetic Proteins / genetics
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Bone Morphogenetic Proteins / metabolism*
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COS Cells
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Chlorocebus aethiops
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / metabolism*
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Genes, Reporter
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Multiprotein Complexes
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Protein Serine-Threonine Kinases / genetics
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Protein Serine-Threonine Kinases / metabolism
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
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Receptors, Growth Factor / genetics
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Receptors, Growth Factor / metabolism
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Receptors, Transforming Growth Factor beta / genetics
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Receptors, Transforming Growth Factor beta / metabolism*
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Signal Transduction / physiology*
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Smad2 Protein
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Trans-Activators / genetics
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Trans-Activators / metabolism
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transforming Growth Factor beta / genetics
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Transforming Growth Factor beta / metabolism*
Substances
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Bone Morphogenetic Proteins
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DNA-Binding Proteins
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Drosophila Proteins
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MAD protein, Drosophila
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Multiprotein Complexes
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Receptors, Cell Surface
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Receptors, Growth Factor
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Receptors, Transforming Growth Factor beta
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Smad2 Protein
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Trans-Activators
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Transcription Factors
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Transforming Growth Factor beta
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myo protein, Drosophila
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wit protein, Drosophila
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tkv protein, Drosophila
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Protein Serine-Threonine Kinases
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Activin Receptors
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Bone Morphogenetic Protein Receptors, Type I