Abstract
The TGF‐β's are multifunctional, pleiotropic molecules with major effects in control of cellular migration, cellular proliferation, and elaboration of extracellular matrix. Thus far, five distinct isoforms of TGF‐β have been described, each approximately 65–85% homologous and containing the characteristic 9 positionally conserved cysteine residues. Although the actions of the activated mature forms of the different isoforms on cells are qualitatively similar in most cases, there are a few examples of distinct activities. For example, TGF‐β's 1 and 3, but not TGF‐β2, inhibit the growth of large vessel endothelial cells, and TGF‐β's 2 and 3, but not TGF‐β1, inhibit the survival of cultured embryonic chick ciliary ganglionic neurons. In addition, selective targeting of the latent forms of the TGF‐β's is suggested by the observation that latent TGF‐β2 is the prominent isoform found in body fluids such as amniotic fluid, breast milk, and the aqueous and vitreous humor of the eye; it is noteworthy in this regard that TGF‐β2 is unique among various isoforms in that it lacks a RGD integrin‐binding sequence in its precursor. The most dramatic differences in the TGF‐β isoforms are seen at the level of expression, where there is now a wealth of data demonstrating both spatially and temporally distinct expression of both the mRNAs and proteins in developing tissues, regenerating tissues, and in pathologic responses. Moreover, the post‐transcriptional regulation of TGF‐β expression by members of the steroid/retinoid family of nuclear receptors is also isoform‐specific; thus, treatment of keratinocytes with retinoids induces secretion of TGF‐β2, whereas treatment of breast cancer cells with gestodene, a synthetic progestin, induces secretion of TGF‐β1. Recent characterization of the 5′ regulatory regions of the human TGF‐β 1, 2, and 3 genes suggests that distinct features of the promoters, including the presence of TATAA boxes and transcription factor binding sites, form the basis for the observed differential transcription. © 1992 Wiley‐Liss, Inc.