2. Academic Validation
  3. Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B

Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B

  • Cell Commun Signal. 2015 Jun 6;13:27. doi: 10.1186/s12964-015-0104-z.
Oddrun Elise Olsen 1,  Karin Fahl Wader 2,  Hanne Hella 3,  Anne Kærsgaard Mylin 4,  Ingemar Turesson 5,  Ingerid Nesthus 6,  Anders Waage 7 8,  Anders Sundan 9 10,  Toril Holien 11
Affiliations

Affiliations

  • 1 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.
  • 2 Departments of Oncology, and Hematology, St. Olav's University Hospital, Trondheim, Norway. Karin.Inger.Martina.Fahl.Wader@stolav.no.
  • 3 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.
  • 4 Department of Haematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. anne.k.mylin@dadlnet.dk.
  • 5 Department of Hematology and Coagulation Disorders, Skane University Hospital, Malmö, Sweden. ingemar.turesson@med.lu.se.
  • 6 Department of Medicine, Haukeland University Hospital, Bergen, Norway. inesthus@broadpark.no.
  • 7 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.
  • 8 Departments of Hematology, St. Olav's University Hospital, Trondheim, Norway. anders.waage@ntnu.no.
  • 9 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.
  • 10 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.
  • 11 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.
PMID: 26047946 DOI: 10.1186/s12964-015-0104-z
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.

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