α2-Macroglobulin: A Binding Protein for Transforming Growth Factor-β and Various Cytokines

Publisher Website
Google Scholar
Abstract
α2-Macroglobulin (α2M) is a large plasma glycoprotein that has long been known as an irreversible inhibitor of a variety of proteinases. More recently, it has been reported that numerous growth factors, cytokines and hormones bind to α2M through diverse mechanisms. We review here a series of observations from our laboratory that support the concept that α2M is a carrier protein for transforming growth factor-β (TGF-β) and allows this factor to act as an autocrine regulator of adrenocortical steroidogenic functions. α2M was found to be synthesized and secreted by primary cultures of bovine adrenocortical cells in fairly large amounts (1 μg/l06 cells/24 h). TGF-β is also secreted by this cell type, although under a latent form. Two distinct latent TGF-β complexes have been characterized in adrenocortical cell conditioned medium, one of which is a complex between α2M and TGF-β. Although α2M prevents the binding of TGF-β to its membrane receptors, long-term incubation of α2M with adrenocortical cells results in inhibition of cortisol production similar to that observed in the presence of TGF-β alone. Taken together, these observations suggest that adrenocortical cells can release active TGF-β from its latent complex with α2M through an unknown mechanism. α2M can therefore be considered as a TGF-β carrier protein.

This publication has 0 references indexed in Scilit: