Transforming growth factor-β (TGF-β) signals by contacting two distantly related transmem-brane serine/threonine kinases called receptors I and II. The role of these molecules in signalling has now been determined. TGF-β binds directly to receptor II, which is a constitutively active kinase. Bound TGF-β is then recognized by receptor I which is recruited into the complex and becomes phosphorylated by receptor II. Phosphorylation allows receptor I to propagate the signal to downstream substrates. This provides a mechanism by which a cytokine can generate the first step of a signalling cascade.