title: Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B.
abstract: BACKGROUND
  Activins are members of the TGF-β family of ligands that have multiple biological functions in embryonic stem cells as well as in differentiated tissue. Serum levels of activin A were found to be elevated in pathological conditions such as cachexia, osteoporosis and cancer. Signaling by activin A through canonical ALK4-ACVR2 receptor complexes activates the transcription factors SMAD2 and SMAD3. Activin A has a strong affinity to type 2 receptors, a feature that they share with some of the bone morphogenetic proteins (BMPs). Activin A is also elevated in myeloma patients with advanced disease and is involved in myeloma bone disease.
  
  
  RESULTS
  In this study we investigated effects of activin A binding to receptors that are shared with BMPs using myeloma cell lines with well-characterized BMP-receptor expression and responses. Activin A antagonized BMP-6 and BMP-9, but not BMP-2 and BMP-4. Activin A was able to counteract BMPs that signal through the type 2 receptors ACVR2A and ACVR2B in combination with ALK2, but not BMPs that signal through BMPR2 in combination with ALK3 and ALK6.
  
  
  CONCLUSIONS
  We propose that one important way that activin A regulates cell behavior is by antagonizing BMP-ACVR2A/ACVR2B/ALK2 signaling.
authors.affiliation: K.G. Jebsen Center for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Post box 8905, MTFS, N-7491, Trondheim, Norway. oddrun.e.olsen@ntnu.no.
authors.forename: Oddrun Elise
authors.initials: OE
authors.lastname: Olsen
authors.affiliation: Departments of Oncology, and Hematology, St. Olav's University Hospital, Trondheim, Norway. Karin.Inger.Martina.Fahl.Wader@stolav.no.
authors.forename: Karin Fahl
authors.initials: KF
authors.lastname: Wader
authors.affiliation: K.G. Jebsen Center for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Post box 8905, MTFS, N-7491, Trondheim, Norway. hanne.hella@ntnu.no.
authors.forename: Hanne
authors.initials: H
authors.lastname: Hella
authors.affiliation: Department of Haematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. anne.k.mylin@dadlnet.dk.
authors.forename: Anne Kærsgaard
authors.initials: AK
authors.lastname: Mylin
authors.affiliation: Department of Hematology and Coagulation Disorders, Skane University Hospital, Malmö, Sweden. ingemar.turesson@med.lu.se.
authors.forename: Ingemar
authors.initials: I
authors.lastname: Turesson
authors.affiliation: Department of Medicine, Haukeland University Hospital, Bergen, Norway. inesthus@broadpark.no.
authors.forename: Ingerid
authors.initials: I
authors.lastname: Nesthus
authors.affiliation: K.G. Jebsen Center for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Post box 8905, MTFS, N-7491, Trondheim, Norway. anders.waage@ntnu.no.|Departments of Hematology, St. Olav's University Hospital, Trondheim, Norway. anders.waage@ntnu.no.
authors.forename: Anders
authors.initials: A
authors.lastname: Waage
authors.affiliation: K.G. Jebsen Center for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Post box 8905, MTFS, N-7491, Trondheim, Norway. anders.sundan@ntnu.no.|CEMIR (Centre of Molecular Inflammation Research), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. anders.sundan@ntnu.no.
authors.forename: Anders
authors.initials: A
authors.lastname: Sundan
authors.affiliation: K.G. Jebsen Center for Myeloma Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Post box 8905, MTFS, N-7491, Trondheim, Norway. toril.holien@ntnu.no.
authors.forename: Toril
authors.initials: T
authors.lastname: Holien
mesh_terms: D030201:Activin Receptors, Type I / Q000378:metabolism; D030301:Activin Receptors, Type II / Q000378:metabolism*; D028341:Activins / Q000378:metabolism*; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D038681:Follistatin / Q000378:metabolism; D006801:Humans; D009101:Multiple Myeloma / Q000378:metabolism*; D060066:Protein Interaction Maps; D015398:Signal Transduction
chemical_list: D019485:Bone Morphogenetic Proteins; D038681:Follistatin; C422405:activin A; D028341:Activins; C425423:ACVR1 protein, human; C579679:ACVR2B protein, human; D030201:Activin Receptors, Type I; D030301:Activin Receptors, Type II; C425585:activin receptor type II-A