The Smads

The Smads are a family of intracellular signalling molecules that act downs tream of receptors for the transforming growth factor (TGF)-beta family of ligands. Three classes of Smads have been identified. The receptor-regulate d Smads are direct substrates for the type I receptors, which are serine/th reonine kinases. Once phosphorylated and activated, these Smads form hetero -oligomeric complexes with a second class of Smad, the common mediator Smad s. These Smad complexes translocate to the nucleus, where they are recruite d to DNA primarily by site-specific DNA binding transcription factors, and participate in regulating the transcription of target genes. Inhibitory Sma ds are the third identified class which antagonise the activity of the rece ptor-regulated Smads. Aberrant TGF-beta signalling has been associated with several human diseases such as cancer and fibrosis. The identification of the Smads as primary transducers of TGF-beta signals raises the possibility that agents directed at modulating Smad activity would have therapeutic ap plications. (C) 1999 Elsevier Science Ltd. All rights reserved.