Differential binding and neutralization of activins A and B by follistatin and follistatin like-3 (FSTL-3/FSRP/FLRG)
Differential binding and neutralization of activins A and B by follistatin and follistatin like-3 (FSTL-3/FSRP/FLRG)
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DOI：
10.1210/en.2002-0203
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发表时间：
2003-05-01
期刊：
影响因子：
4.8
通讯作者：
Sidis, Y
中科院分区：
文献类型：
--
作者：
Schneyer, A;Schoen, A;Sidis, Y
激活素和其他 TGFbeta 超家族信号传导的调节是卵泡抑素 (FS) 和 FS 样 3 (FSTL-3) 的主要作用机制。然而，大多数这些配体的研究都使用激活素 A，因为它具有广泛的可用性。我们现在已经测试了 FS288 和 FSTL-3 相对于激活素 A 结合和中和激活素 B 的能力。激活素 B 与 FS 和 FSTL-3 的结合效力大约比激活素 A 低 10 倍。此外，虽然两种激活素在 293 细胞报告基因测定中具有相似的生物活性，但 FS 和 FSTL-3 相对于激活素 B 中和激活素 A 的效率大约高一倍。结果表明，FS 和 FSTL-3 对激活素 A 和 B 的中和作用并不相同，因此在产生这两种激活素的组织（例如卵巢）中，每种激活素的相对活性可能有很大不同。此外，可能需要重新评估主要使用激活素 B 但已使用激活素 A 进行体外检查的生物系统，以确定 FS 或 FSTL-3 的实际生理作用。
Modulation of activin and other TGFbeta superfamily signaling is the primary mechanism of action for both follistatin (FS) and FS-like 3 (FSTL-3). However, most studies of these ligands use activin A due to its wide availability. We have now tested the ability of FS288 and FSTL-3 to bind and neutralize activin B relative to activin A. Activin B bound to both FS and FSTL-3 at a potency approximately 10-fold lower than that of activin A. Moreover, whereas both activins had similar biological activity in 293 cell reporter assays, FS and FSTL-3 were approximately fold more effective in neutralizing activin A relative to activin B. These results suggest that neutralization of activins A and B by FS and FSTL-3 are not identical, so that the relative activity of each activin in tissues where both are produced, such as in the ovary, could be quite different. In addition, biological systems that use primarily activin B, but which have been examined in vitro using activin A, may need to be reevaluated to determine the actual physiologic roles of FS or FSTL-3.