Transforming Growth Factor-βs: A Multifunctional Cytokine Family

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Abstract
Knowledge of the structure of the first recognized transforming growth factor-β (TGF-β1) has led to the identification of more than two dozen structurally related peptides which appear of crucial importance in the regulation of cell proliferation, cell differentiation and embryogenesis. TGF-β1 and its close homologs (TGFβ2-5) are multifunctional peptides whose effects on cell functions are dependent upon the cell type, the environment and the presence of other growth factors. TGF-β1 is produced and secreted as a latent macromolecular complex. One of the major steps in the control of TGF-β activity may thus be its release (activation) from its latent form upon the effect of local factors. Adrenocortical cells may be taken as an example in which autocrine production of TGF-β may be a component of a negative regulatory loop in balance with the positive effect of a systemic hormone (ACTH) in controlling the expression of the cell steroidogenic differentiated functions. In this system, latent TGF-β can be activated by an ACTH-induced secreted protein (CISP), a member of the thrombospondin family. This points to the importance of the functional interaction between TGF-βs and extracellular matrix components in the local regulation of cell activities.

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