The TGF-beta superfamily comprises several different extracellular factors. The factors bind to and activate the membrane-bound TGF-beta receptor, which is a serine-threonine kinase. Autophosphorylated and thereby activated TGF-beta receptor activates Smad proteins, which transmit the signal from the membrane to the nucleus, where Smads bind to DNA and activate or inhibit gene expression. The gene coding for the TGF-beta receptor is mutated in many human cancers, including tumors of the colon and the stomach.