Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B

Cell Communication and Signaling

Research Article

Anne Kærsgaard Mylin¹  Ingemar Turesson²  Ingerid Nesthus³  Karin Fahl Wader⁴  Hanne Hella⁵  Toril Holien⁵  Oddrun Elise Olsen⁵  Anders Sundan⁶  Anders Waage⁷ 

[1] Department of Haematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark;Department of Hematology and Coagulation Disorders, Skane University Hospital, Malmö, Sweden;Department of Medicine, Haukeland University Hospital, Bergen, Norway;Departments of Oncology, and Hematology, St. Olav’s University Hospital, Trondheim, Norway;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;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;CEMIR (Centre of Molecular Inflammation Research), Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway;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;Departments of Hematology, St. Olav’s University Hospital, Trondheim, Norway;

关键词: Activin A;    Follistatin;    Receptor;    BMP;    Bone morphogenetic proteins;    Myeloma;   

DOI  :  10.1186/s12964-015-0104-z

 received in 2015-01-26, accepted in 2015-04-22,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundActivins 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.ResultsIn 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.ConclusionsWe propose that one important way that activin A regulates cell behavior is by antagonizing BMP-ACVR2A/ACVR2B/ALK2 signaling.

【 授权许可】

CC BY   
© Olsen et al. 2015