The Drosophila type II receptor, Wishful thinking, binds BMP and myoglianin to activate multiple TGFbeta family signaling pathways

FEBS Lett. 2005 Aug 29;579(21):4615-21. doi: 10.1016/j.febslet.2005.06.088.

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

  • Activin Receptors / genetics
  • Activin Receptors / metabolism
  • Animals
  • Bone Morphogenetic Protein Receptors, Type I
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism*
  • COS Cells
  • Chlorocebus aethiops
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Genes, Reporter
  • Multiprotein Complexes
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Receptors, Growth Factor / genetics
  • Receptors, Growth Factor / metabolism
  • Receptors, Transforming Growth Factor beta / genetics
  • Receptors, Transforming Growth Factor beta / metabolism*
  • Signal Transduction / physiology*
  • Smad2 Protein
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism*

Substances

  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • Drosophila Proteins
  • MAD protein, Drosophila
  • Multiprotein Complexes
  • Receptors, Cell Surface
  • Receptors, Growth Factor
  • Receptors, Transforming Growth Factor beta
  • Smad2 Protein
  • Trans-Activators
  • Transcription Factors
  • Transforming Growth Factor beta
  • myo protein, Drosophila
  • wit protein, Drosophila
  • tkv protein, Drosophila
  • Protein-Serine-Threonine Kinases
  • Activin Receptors
  • Bone Morphogenetic Protein Receptors, Type I