Transforming growth factor beta (TGFβ) is the lead of a large family of factors studied in this chapter, which comprise several stricto sensu TGFβs and a subfamily of related factors, and a subfamily of bone morphogenetic factors (BMPs). The receptors of these factors display serine/threonine kinase activity, which distinguishes them from those presenting (or are associated to) tyrosine kinase activity (Chaps. 1 and 4). They are involved in many cellular processes, especially during development, and play a role in cell survival, proliferation and differentiation, as well as in cell adhesion and motility, and its alterations are found in cancer, inflammation and fibrosis. Overall, the TGFβ pathway generally works in opposition to cell proliferation and plays a tumour suppressor role counteracting oncogenesis, but the role of this pathway is ambivalent since it frequently enhances cell motility and migration, participates to the epithelial-to-mesenchymal transition and, consequently, may favour metastasis dissemination.

The factors of the TGFβ family are active as homodimers and are responsible of the formation, at the level of the target cell, of a hexameric complex made of two molecules of ligand, two molecules of type I receptors and two molecules of type II receptors, in addition to coreceptors required for signalling. Once activated by ligand binding, type II receptors phosphorylate type I receptors, which in turn phosphorylate transcription factors of the SMAD family. This denomination comes from the names of the ortholog genes sma (small) of Caenorhabditis elegans and mad (mothers against decapentaplegic homologue) of drosophila. The SMAD factors bind to a common interactant, also of the SMAD family, and form a transcriptional activator or repressor complex which is able to relocate to the nucleus and regulate the transcription of target genes, which are more or less specific of the extracellular factor generating the signal.