PathwayStep110 PathwayStep109 Phosphorylated SMAD2 and SMAD3 form a complex with SMAD4 The SMAD2/3:SMAD4 complex transfers to the nucleus Phosphorylation of SMAD2/3 by Activin:Activin Receptor ACVR2A/B (ActRIIA/B) Phosphorylates ACVR1C (ActRIC, ALK7) in Response to Activin Phospho R-SMAD(SMAD2/3):CO-SMAD(SMAD4):FOXH1 Binds Activin Response Element Activin A/AB/B Binds Activin Receptor ACVR2A/B:ACVR1B Activin AB/B Binds Activin Receptor ACVR2A/B:ACVR1C ACVR2A/B (ActRIIA/B) Phosphorylates ACVR1B (ActRIB, ALK4) in Response to Activin PathwayStep5938 PathwayStep5933 PathwayStep5932 PathwayStep5931 PathwayStep5930 PathwayStep5935 PathwayStep5934 Antagonism of Activin by Follistatin 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. Authored: May, B, 2011-08-23 Edited: May, B, 2011-08-23 Pubmed16636301 Pubmed22651914 Pubmed8622651 Pubmed8721982 Reactome Database ID Release 431502540 Reactome, http://www.reactome.org ReactomeREACT_150238 Reviewed: Chen, Ye-Guang, 2012-11-14