Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B.

Autor: Olsen OE; 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., Wader KF; Departments of Oncology, and Hematology, St. Olav's University Hospital, Trondheim, Norway. Karin.Inger.Martina.Fahl.Wader@stolav.no., Hella H; 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., Mylin AK; Department of Haematology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. anne.k.mylin@dadlnet.dk., Turesson I; Department of Hematology and Coagulation Disorders, Skane University Hospital, Malmö, Sweden. ingemar.turesson@med.lu.se., Nesthus I; Department of Medicine, Haukeland University Hospital, Bergen, Norway. inesthus@broadpark.no., Waage A; 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., Sundan A; 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., Holien T; 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.
Jazyk: angličtina
Zdroj: Cell communication and signaling : CCS [Cell Commun Signal] 2015 Jun 06; Vol. 13, pp. 27. Date of Electronic Publication: 2015 Jun 06.
DOI: 10.1186/s12964-015-0104-z
Abstrakt: 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.
Databáze: MEDLINE
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