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GDF11 activates Smad and non-Smad signals to affect gene expression. The GDF11 signaling pathway is modulated by multiple proteins as negative feedback loops. WFIKKN1/2, FSTL3, and pro-peptide proteins inhibit GDF11 signal pathway at various points in the extracellular compartment. In the intracellular compartment, GDF11 signaling is modulated by the inhibitory Smad proteins (I-Smad, Smad7).
