INSERM UMR866, Université de Bourgogne, Facultés des Sciences de Santé, 7 Boulevard Jeanne d'Arc, 21033 Dijon Cedex, France.
INSERM UMR866, Université de Bourgogne, Facultés des Sciences de Santé, 7 Boulevard Jeanne d'Arc, 21033 Dijon Cedex, France.
Pharmacol Ther. 2015 Dec;156:26-33. doi: 10.1016/j.pharmthera.2015.10.006. Epub 2015 Oct 30.
Members of the TGF-β superfamily transduce their signals through type I and II receptor serine/threonine kinases. The regulation of members of the TGF-β family is known to be complex, because many proteins able to bind the ligands and inhibit their activities have been identified. Growth and differentiation factor 11 (Gdf11) as activins belong to the TGF-β family. GDF11, like other members of the TGF-β superfamily, is produced from precursor proteins by proteolytic processing. The binding of activins to activin type IIA (ActRIIA) or type IIB (ActRIIB) receptors induces the recruitment and phosphorylation of an activin type I receptor which then phosphorylates the Smad2 and Smad3 intracellular signaling proteins. GDF11 signal through the ActRIIB pathway. Recent studies have reported that GDF11-ActRIIB-Smad2/3-dependent signaling is a key regulatory mechanism in proliferating erythroid precursors as it controls their late-stage maturation. The administration of GDF11 is effective in experimental cardiac hypertrophy, and the identification of GDF11 as a "rejuvenating factor" opens up perspectives for the treatment of age-related cardiac dysfunction. Recent studies of the heart indicate that exposure to young blood reverses age-related impairments. GDF11 could be one of the circulating molecules that influence the aging of different tissues. Is GDF11 an "elixir of youth"?
TGF-β 超家族成员通过 I 型和 II 型受体丝氨酸/苏氨酸激酶转导其信号。已知 TGF-β 家族成员的调节非常复杂，因为已经鉴定出许多能够结合配体并抑制其活性的蛋白质。生长分化因子 11（Gdf11）作为激活素属于 TGF-β 家族。GDF11 与 TGF-β 超家族的其他成员一样，由前体蛋白通过蛋白水解加工产生。激活素与激活素 IIA（ActRIIA）或 IIB 型受体（ActRIIB）的结合诱导激活素 I 型受体的募集和磷酸化，然后磷酸化 Smad2 和 Smad3 细胞内信号蛋白。GDF11 通过 ActRIIB 途径发出信号。最近的研究报道，GDF11-ActRIIB-Smad2/3 依赖性信号是增殖性红系前体的关键调节机制，因为它控制其晚期成熟。GDF11 的给药在实验性心肌肥厚中是有效的，并且将 GDF11 鉴定为“返老还童因子”为治疗与年龄相关的心脏功能障碍开辟了新的视角。最近对心脏的研究表明，接触年轻血液可以逆转与年龄相关的损伤。GDF11 可能是影响不同组织衰老的循环分子之一。GDF11 是“青春之泉”吗？
