“…While seven Smad genes have been reported in the literature thus far, they can be classi®ed into three types according to their functions, i.e., receptor-activated Smads (Smad1 and Smad5 for BMP; Smad2 and Smad3 for TGF-b and activin), co-Smad (Smad4) and anti-Smads (Smad6 and Smad7) Derynck et al, 1996;Eppert et al, 1996;Gra et al, 1996;Hahn et al, 1996;Hayashi et al, 1997;Hoodless et al, 1996;Lechleider et al, 1996;Liu et al, 1996;Riggins et al, 1996;Thomsen, 1996;Topper et al, 1997;Yingling et al, 1996;Zhang et al, 1996). Smad2 and Smad3, the receptor-activated, TGFb signaling Smads, are known to be highly homologous with regard to amino acid sequence and structural characteristics, and both have been found to mediate TGF-b and activin signals by forming heteromers with Smad4 (Eppert et al, 1996;Gra et al, 1996;Riggins et al, 1996;Wrana and Pawson, 1997;Zhang et al, 1996). Despite extensive studies of the Smad gene family, however, no de®nitive di erences in the regulations or functions of these receptor-activated Smads have been identi®ed.…”