The transforming growth factor-β or TGF-β signaling pathway regulates cell proliferation and differentiation. It starts with the homodimeric serine/threonine kinase receptors—TGF-β receptors types one and two. The dimeric protein, TGF-β, binds the type II TGF-β receptors, which recruit adjacent type I receptors and phosphorylates them, forming an active tetrameric complex. The activated TGF-β type I receptors recruit a transcriptional regulator called receptor-activated Smad or R-Smad and phosphorylate it. The phosphorylated R-Smad undergoes a conformational change and dissociates from the receptor. Two R-Smads dimerize and bind an unphosphorylated co-Smad forming a trimeric Smad complex. The Smad complex is transported to the nucleus, where it binds a nuclear transcription factor and regulates the transcription of a target gene. Once a nuclear phosphatase dephosphorylates the R-Smads, the complex disassembles, and the Smads are translocated back to the cytosol.