Members of the Smad protein family are fundamental downstream mediators of TGF-beta signals. However, the basic, linear Smad signaling pathway is unlikely to be the sole contributor to the plethora of cell type-specific TGF-beta responses. Investigators have identified a number of molecules that interact with the TGF-beta receptors (TbetaRs) and may explain, at least in part, the tight regulation of TGF-beta effects. Understanding these TbetaR-interacting molecules is thus a matter of great potential significance for elucidating TGF-beta-family signal transduction. The present article reviews our current understanding of the roles and mechanisms of action of this relatively understudied group of molecules.
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