The Drosophila activin receptor baboon signals through dSmad2 and controls cell proliferation but not patterning during larval development.
The TGF-beta superfamily of growth and differentiation factors, including TGF-beta, 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-beta/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-beta/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-beta pathway that is analogous to its vertebrate counterpart and show that this pathway functions to promote cellular growth with minimal effects on patterning.
Brummel
T
T
Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697, USA.
Abdollah
S
S
Haerry
T E
TE
Shimell
M J
MJ
Merriam
J
J
Raftery
L
L
Wrana
J L
JL
O'Connor
M B
MB
D029404:Activin Receptors; D030201:Activin Receptors, Type I; D000595:Amino Acid Sequence; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000235:genetics; D002455:Cell Division; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics*; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins; D018507:Gene Expression Regulation, Developmental; D017403:In Situ Hybridization; D007814:Larva / Q000235:genetics / Q000254:growth & development*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D017978:Receptors, Growth Factor / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D015398:Signal Transduction / Q000502:physiology*; D051899:Smad2 Protein; D015534:Trans-Activators / Q000737:chemistry / Q000235:genetics*; D014921:Wings, Animal / Q000254:growth & development
D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; D017978:Receptors, Growth Factor; D051899:Smad2 Protein; D015534:Trans-Activators; D029404:Activin Receptors; D030201:Activin Receptors, Type I; C517157:Babo protein, Drosophila