Signaling by Activin

Activin was initially discovered as an activator of follicle stimulating hormone in the pituitary gland. It has since been shown to be an important participant in the differentiation of embryonic cells into mesodermal and endodermal layers. Activin binds the Activin receptor and triggers downstream events: phosphorylation of SMAD2 and SMAD3 followed by activation of gene expression (reviewed in Attisano et al. 1996, Willis et al. 1996, Chen et al. 2006, Hinck 2012). Activins are dimers comprising activin A (INHBA:INHBA), activin AB (INHBA:INHBB), and activin B (INHBB:INHBB). Activin first binds the type II receptor (ACVR2A, ACVR2B) and this complex then interacts with the type I receptor (ACVR1B, ACVR1C) (Attisano et al. 1996). The type II receptor phosphorylates the type I receptor and then the phosphorylated type I receptor phosphorylates SMAD2 and SMAD3. Dimers of phosphorylated SMAD2/3 bind SMAD4 and the resulting ternary complex enters the nucleus and activates target genes.

活化素最初被发现为垂体腺中促卵泡激素的激活剂。此后，研究表明其在胚胎细胞分化为间充质和内胚层过程中扮演着至关重要的角色。活化素与活化素受体结合，进而引发下游事件：SMAD2和SMAD3的磷酸化，随后激活基因表达（参见Attisano等人的1996年、Willis等人的1996年、Chen等人的2006年以及Hinck的2012年综述）。活化素由活化素A（INHBA:INHBA）、活化素AB（INHBA:INHBB）和活化素B（INHBB:INHBB）二聚体组成。活化素首先与II型受体（ACVR2A、ACVR2B）结合，随后此复合物与I型受体（ACVR1B、ACVR1C）相互作用（参见Attisano等人的1996年）。II型受体磷酸化I型受体，随后磷酸化的I型受体再磷酸化SMAD2和SMAD3。磷酸化的SMAD2/3二聚体与SMAD4结合，形成的三元复合物进入细胞核并激活靶基因。