Transforming growth factor-β (TGF-β) is a family of 25-kDa dimeric proteins that regulate the cellular growth and differentiation, the formation of extracellular matrix, and the immune function. TGF-βs belong to a larger family of structurally related proteins known as the TGF-β superfamily, which includes activins and bone morphogenetic proteins. TGF-β exerts the effects through binding to type I (TβR-I; 53 kDa) and type II (TβR-II; 75 kDa) serine/threonine kinase receptors. Overall structures of TβR-I and TβR-II are similar to each other. Preceding the kinase domain of TβR-I, there is a region termed the GS domain, which is conserved in type I receptors, but not in type II receptors. After ligand binding, TβR-I and TβR-II form a heteromeric receptor complex, which is most likely a heterotetramer composed of two molecules each of TβR-I and TβR-II. TβR-II transphosphorylates the GS domain of TβR-I, which then activates the TβR-I kinase and transduces signals. By yeast two-hybrid system, several proteins which interact with type I or type II receptors, and possibly transduce the signals for TGF-p, have been isolated. Mutations in the TβR-II gene have been identified in several carcinoma cells, which suggests that loss of the TβR-II protein is one of the mechanisms by which cancer cells acquire resistance to the growth inhibitory activity of TGF-β.