Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B

被引：125

作者：

Olsen, Oddrun Elise ^{[1
]}

Wader, Karin Fahl ^{[2
,3
]}

Hella, Hanne ^{[1
]}

Mylin, Anne Kaersgaard ^{[4
]}

Turesson, Ingemar ^{[5
]}

Nesthus, Ingerid ^{[6
]}

Waage, Anders ^{[1
,3
]}

Sundan, Anders ^{[1
,7
]}

Holien, Toril ^{[1
]}

机构：

[1] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, KG Jebsen Ctr Myeloma Res, MTFS, N-7491 Trondheim, Norway

[2] St Olavs Univ Hosp, Dept Oncol, Trondheim, Norway

[3] St Olavs Univ Hosp, Dept Hematol, Trondheim, Norway

[4] Univ Copenhagen, Rigshosp, Dept Haematol, DK-2100 Copenhagen, Denmark

[5] Skane Univ Hosp, Dept Hematol & Coagulat Disorders, Malmo, Sweden

[6] Haukeland Hosp, Dept Med, N-5021 Bergen, Norway

[7] Norwegian Univ Sci & Technol, Dept Canc Res & Mol Med, CEMIR, Ctr Mol Inflammat Res, N-7491 Trondheim, Norway

来源：

CELL COMMUNICATION AND SIGNALING | 2015年 / 13卷

关键词：

Activin A; Follistatin; Receptor; BMP; Bone morphogenetic proteins; Myeloma; BONE MORPHOGENETIC PROTEINS; MULTIPLE-MYELOMA; INDUCE APOPTOSIS; GROWTH; RECEPTORS; FOLLISTATIN; POTENT; CELLS;

D O I：

10.1186/s12964-015-0104-z

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Background: Activins are members of the TGF-beta 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.

引用

页数：7

共 20 条

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