title: Hyperactive BMP signaling induced by ALK2(R206H)  requires type II receptor function in a Drosophila model for classic fibrodysplasia ossificans progressiva.
abstract: BACKGROUND
  Fibrodysplasia Ossificans Progressiva (FOP) is an autosomal dominant disorder characterized by episodic deposition of heterotopic bone in place of soft connective tissue. All FOP-associated mutations map to the BMP type I receptor, ALK2, with the ALK2(R206H) mutant form found in the vast majority of patients. The mechanism(s) regulating the expressivity of hyperactive ALK2(R206H) signaling throughout a patient's life is not well understood.
  
  
  RESULTS
  In Drosophila, human ALK2(R206H) receptor induces hyperactive BMP signaling. As in vertebrates, elevated signaling associated with ALK2(R206H) in Drosophila is ligand-independent. We found that a key determinant for ALK2(R206H) hyperactivity is a functional type II receptor. Furthermore, our results indicate that like its Drosophila ortholog, Saxophone (Sax), wild-type ALK2 can antagonize, as well as promote, BMP signaling.
  
  
  CONCLUSIONS
  The dual function of ALK2 is of particular interest given the heterozygous nature of FOP, as the normal interplay between such disparate behaviors could be shifted by the presence of ALK2(R206H) receptors. Our studies provide a compelling example for Drosophila as a model organism to study the molecular underpinnings of complex human syndromes such as FOP.
authors.affiliation: Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, Rhode Island 02912, USA.
authors.forename: Viet Q
authors.initials: VQ
authors.lastname: Le
authors.forename: Kristi A
authors.initials: KA
authors.lastname: Wharton
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D052006:Bone Morphogenetic Protein Receptors, Type II / Q000235:genetics / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000502:physiology*; D006801:Humans; D009221:Myositis Ossificans / Q000503:physiopathology*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D014921:Wings, Animal / Q000033:anatomy & histology / Q000502:physiology
chemical_list: D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D018125:Receptors, Transforming Growth Factor beta; C086338:sax protein, Drosophila; D030201:Activin Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II