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

Abstract

The TGF-␤ superfamily of growth and differentiation factors, including TGF-␤, 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-␤/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-␤/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-␤ pathway that is analogous to its vertebrate counterpart and show that this pathway functions to promote cellular growth with minimal effects on patterning.

Comparative transcriptomics across 14 Drosophila species reveals signatures of longevity

“…Among them were several cell surface receptors and signaling molecules, such as Fas2 , which codes for a cell adhesion protein Fasciclin 2 that interacts with semaphorin (Smad) and connectin to regulate axon fasciculation (Yu, Huang & Kolodkin, 2000); babo , which codes for a type I activin receptor and regulates cell proliferation by stimulating Smad2‐dependent pathways (Brummel et al., 1999); and shark , which codes for SH2 ankyrin repeat tyrosine‐protein kinase and is required for dorsal closure during development (Fernandez et al., 2000). Also present were component of gap junction ( ogre ) and TGF‐beta receptor ( tkv ).…”

E1A Inhibits Transforming Growth Factor-β Signaling through Binding to Smad Proteins

“…Smads 6 and 7 belong to Anti-Smads. In Drosophila, Mad responds to Decapentaplegic (Dpp), a BMPlike ligand, whereas dSmad2 propagates TGF-␤/activin-like signals (6,7). Medea is a Co-Smad, and Dad is an Anti-Smad.…”

Retroactive, a membrane‐anchored extracellular protein related to vertebrate snake neurotoxin‐like proteins, is required for cuticle organization in the larva of Drosophila melanogaster

“…Wishful thinking (Wit) plays a central role in regulation of neuromuscular synapse formation (Aberle et al, 2002;Marques et al, 2002). Finally, Baboon (Babo) regulates cell proliferation during larval development (Brummel et al, 1999). Overall, there is no evidence that these proteins may be involved in cuticle differentiation.…”