The Life Story of TGFβs superfamily: from the beginning to the end

TGFβ-superfamily consists a plethora of extracellular growth factors, modulating developmental procedures and homeostasis in vertebrates and invertebrates. TGFβ-superfamily ligands, synthesized as the large inactive precursors, transform into active ligands following by their interaction with extracellular proteolytic enzymes. Principally, TGFβs ligation to their responsive receptors can trigger two distinct transduction cascades, including 1- SMAD dependent or canonical pathway and 2- SMAD independent or non-canonical ones. R-SMADs are substrates for the type I receptors, as their GS domains act as a docking site for R-SMADs. In the canocical pathway, upon phosphorylation of SSXS of MH2, two phosphorylated-SMADs (P-SMADs) in accordance with receptor tetra-dimerization, homo or heterodimerize and then form a trimer complex by SMAD4. The trimers translocate to the nucleus, where in association with other transcription factors (activators and repressors) modulate their target genes expression. The purpose of this review is to provide a comprehensive information about these cascades and their downstream effectors with an emphasis on the canonical one.