Smad signalling network.

Dimeric ligands of the transforming growth factor β (TGF-β) superfamily bind with high affinity to type II and type I receptor serine/threonine kinases on the cell surface and induce hetero-tetrameric receptor complexes. In such complexes, constitutively auto-phosphorylated type II receptors (green) trans-phosphorylate (arrows) the type I receptor (blue) GS domain. Activated receptors recruit adaptors such as disabled-2 (Dab-2) and sortin nexin 6 (SNX6) that positively affect signal transduction. Small GTPases such as Rab5 catalyse movement of activated receptor complexes to early endosomal compartments, where they encounter phospholipid-bound carriers such as SARA that assist in presentation of the major signalling effectors, the Smads, to the type I receptor kinase. Smads can be anchored in the cytoplasm onto microtubules and actin-binding proteins such as filamin, but the role of the cytoskeleton in Smad signalling is presently unclear (broken arrows).