The Drosophila activin receptor Baboon signals through dSmad2 and controls cell proliferation but not patterning during larval development

Ted Brummel, Shirin Abdollah, Theodor E. Haerry, Mary Jane Shimell, John Merriam, Laurel Raftery, Jeffrey L. Wrana, Michael B. O'Connor

Research output: Contribution to journalArticlepeer-review

150 Scopus citations

Abstract

The TGF-β superfamily of growth and differentiation factors, including TGF-β, Activins and bone morphogenetic proteins (BMPs) play critical roles in regulating the development of many organisms. These factors signal through a heteromeric complex of type I and II serine/threonine kinase receptors that phosphorylate members of the Smad family of transcription factors, thereby promoting their nuclear localization. Although components of TGF-β/Activin signaling pathways are well defined in vertebrates, no such pathway has been clearly defined in invertebrates. In this study we describe the role of Baboon (Babo), a type I Activin receptor previously called Atr-I, in Drosophila development and characterize aspects of the Babo intracellular signal-transduction pathway. Genetic analysis of babo loss-of-function mutants and ectopic activation studies indicate that Babo signaling plays a role in regulating cell proliferation. In mammalian cells, activated Babo specifically stimulates Smad2-dependent pathways to induce TGF-β/Activin- responsive promoters but not BMP-responsive elements. Furthermore, we identify a new Drosophila Smad, termed dSmad2, that is most closely related to vertebrate Smads 2 and 3. Activated Babo associates with dSmad2 but not Mad, phosphorylates the carboxy-terminal SSXS motif and induces heteromeric complex formation with Medea, the Drosophila Smad4 homolog. Our results define a novel Drosophila Activin/TGF-β pathway that is analogous to its vertebrate counterpart and show that this pathway functions to promote cellular growth with minimal effects on patterning.

Original languageEnglish (US)
Pages (from-to)98-111
Number of pages14
JournalGenes and Development
Volume13
Issue number1
DOIs
StatePublished - Jan 1 1999

Keywords

  • Activin
  • Baboon
  • DSmad2
  • Imaginal disc
  • Optic proliferation centers
  • TGF-β

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