The Drosophila Activin receptor Baboon signals through dSmad2 and controls cell proliferation but not patterning during larval development
- Ted Brummel1,7,
- Shirin Abdollah2,
- Theodor E. Haerry1,6,
- Mary Jane Shimell1,6,
- John Merriam3,
- Laurel Raftery4,
- Jeffrey L. Wrana2, and
- Michael B. O’Connor1,5,6,8
- 1Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697 USA; 2Program in Developmental Biology, The Hospital for Sick Children, and Department of Medical Genetics and Microbiology, University of Toronto, Toronto, Canada M5G 1X8; 3Department of Biology, University of California, Los Angeles, California 90024 USA; 4The Cutaneous Biology Research Center, Massachusetts General Hospital, Charlestown, Massachusetts 02129 USA; 5The Howard Hughes Medical Institute, 6Department of Genetics and Cell Biology, University of Minnesota, St. Paul, Minnesota 55108 USA
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 newDrosophila 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 DrosophilaActivin/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.
