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Extra- and intra-cellular regulation of activin A signaling. (A) Activin A is tightly regulated at the extracellular level by both extracellular matrix (follistatin-288, follistatin-315, follistatin-related protein, α2-macroglobin, left-right determination factor 1 (Lefty1), inhibin A) and membrane-bound proteins (betaglycan, Cripto, BAMBI, INHBP/inhibin B, follistatin-288). (B) In the cytoplasm, canonical activin A signaling is controlled during each step of the Smad cascade.
