Fig. 4. Smad signalling centres. Pictorial representation of early signalling events of the Smad pathway. A possible but not yet fully documented signalling scenario is shown, initiating at the plasma membrane. R-Smads (S) anchored to microtubules or filamin become mobilised towards SARA and the receptors where multiprotein centres are organised with the aid of scaffolding proteins containing PDZ domains such as ARIPs (PDZ), additional but yet unknown adaptors (Ad) and R-Smad and Smad4 (S4) anchors-activators such as axin and TRAP-1, respectively. This results in R-Smad phosphorylation and R-Smad–Co-Smad oligomerisation. It is worth noting that a similar signalling scenario might become organised at early endosomes, immediately after receptor-mediated endocytosis. For references see Dong et al. and others (Dong et al., 2000; Furuhashi et al., 2001; Sasaki et al., 2001; Tsuchida et al., 2001; Tsukazaki et al., 1998; Wurthner et al., 2001).