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. 2002 Sep 9;87(6):630–634. doi: 10.1038/sj.bjc.6600511

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Copyright © 2002 Cancer Research UK

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SMADS in the TGFβ/BMP signalling pathway: (i) receptor-activated (ra)-SMADs SMAD2 or SMAD3 are serine-phosporylated upon TGFβ-receptor interaction, whereas SMAD1, SMAD5 or SMAD8 phosphorylation is exclusively induced by BMPs; (ii) SMAD4, the common and unique co-SMAD signalling mediator to all TGFβ/BMP cytokines, heteropolymerises with activated ra-SMADs and migrates to the nucleus where it associates with tissue specific transcription factors (TF); (iii) anti-SMADs produced upon cytokine induction (SMAD7 for TGFβ and SMAD6 for BMPs) block ra-SMAD serine phosphorylation. This inducible negative feedback loop provides a transient response to cytokine activation (see Kretschmar and Massagué, 1999). Extracytoplasmic (EC), cytoplasmic (CP) and nuclear (N) compartments are indicated.