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Cell Commun Signal. 2015 Jun 6;13:27. doi: 10.1186/s12964-015-0104-z.

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

Author information

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.

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.

PMID:
26047946
PMCID:
PMC4467681
DOI:
10.1186/s12964-015-0104-z
[Indexed for MEDLINE]
Free PMC Article

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