[Function, molecular structure and gene expression regulation of transforming growth factor-beta (TGF-beta)]

Transforming growth factor-beta (TGF-beta) is a multifunctional peptide growth factor widely distributed in vertebrates and represents a prototype of a large family of structurally related factors that regulate various cellular functions, ranging from amphibian embryonal development to hormone production in the human pituitary. TGF-beta is a disulfide-bonded homodimer of a subunit of 12.5 kD that is derived from a much larger precursor. The amino acid sequences of TGF-betas are highly conserved among species, suggesting their physiological importance. TGF-beta was originally isolated from human platelets as a factor that induces anchorage-independent growth of normal fibroblasts. However, later studies have revealed that its major biological activities include inhibition of cell proliferation, and regulation of differentiation, cell adhesion and extracellular matrix deposition. There are three types of cellular receptors that bind TGF-beta. Type II receptor, of which cDNA was recently cloned, is a functional serine/threonine kinase and is thought to be involved in the TGF-beta-mediated signal transduction pathway. The importance of TGF-beta in clinical medicine will increase not only as it is a promising therapeutic drug, but also as its excessive activity can be the cause of various human fibrotic diseases.