Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B.
Activin A inhibits BMP-signaling by binding ACVR2A and ACVR2B.
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DOI：
10.1186/s12964-015-0104-z
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发表时间：
2015-06-06
期刊：
影响因子：
--
通讯作者：
Holien T
中科院分区：
文献类型：
--
作者：
Olsen OE;Wader KF;Hella H;Mylin AK;Turesson I;Nesthus I;Waage A;Sundan A;Holien T
活化素是在胚胎干细胞中具有多个生物学功能的TGF-β家族的成员，以及在病理状况中，血清中的血清水平升高激活素A通过规范ALK4-ACVR2受体复合物激活转录因子Smad2和Smad3。受体，它们与某些骨形态发生蛋白（BMP）共享的特征在患有晚期疾病的骨髓瘤患者中也升高。
在这项研究中，我们研究了使用具有良好特征的BMP受体表达和反应的骨髓瘤细胞系与BMP共享的受体的影响。 -4。 BMPR2与ALK3和ALK6结合使用。
我们提出，激活素A的一种重要方法是拮抗BMP-ACVR2A/ACVR2B/ALK2信号传导。
本文的在线版本（DOI：10.1186/S12964-015-0104-Z）包含补充材料，可供授权用户使用。
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. 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. We propose that one important way that activin A regulates cell behavior is by antagonizing BMP-ACVR2A/ACVR2B/ALK2 signaling. The online version of this article (doi:10.1186/s12964-015-0104-z) contains supplementary material, which is available to authorized users.
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