The Transforming Growth Factor-βs

Abstract

Following the initial purification and characterization of transforming growth factor-β (TGF-β) as a homodimeric, 25-kDa peptide (Frolik et al. 1983; Assoian et al. 1983; Roberts et al. 1983 a), there has been an exponential increase in knowledge relating to this molecule. The cloning of TGF-βl and the resultant elucidation of its precursor structure (Derynck et al. 1985) have led to the identification of at least four other forms of TGF-β and the definition of a larger gene family comprising many other structurally related, but functionally distinct, regulatory proteins. The original narrow definition of TGF-β,in terms of induction of a transformed phenotype in mesenchymal cells (Moses et al. 1981; Roberts et al. 1981, 1983 b), has now been supplanted by the knowledge that this peptide affects many functions in nearly all cells. Immunohistochemical and in situ hybridization studies have identified in vivo sites of TGF-β action; its broad spectrum of cellular targets as well as its multifunctional actions suggest that it has a pivotal control function in many physiological and pathological processes. Elucidation of physiological mechanisms of activation of the latent forms of the TGF-βs and of regulation of expression of the TGF-βs and their receptors are important problems that must still be solved for better understanding of the action of the TGF-βs. In this chapter we summarize current knowledge of the chemistry and complex biology of the growing family of TGF-βs.