Smads are the central component in transforming growth factor-beta signaling.

Until recently, little was known about how transforming growth factor (TGF)-beta signals are transduced to the nucleus. With the discovery of the Smad proteins initially in Drosophila and C. elegans, the unraveling of the pathway has begun. Nine different vertebrate members also have been reported, indicating that Smads are a conserved component of the TGF-beta pathway. Currently, there are three functional classes of Smads. Class I Smads are phosphorylated by TGF-beta receptors and move to the nucleus. The Class II Smads function with Class I Smads, while Class III Smads antagonize the function of Class I Smads. New evidence shows that Smads bind specific DNA sequences and induce transcription of downstream target genes, thus placing the Smads at the center of the TGF-beta signaling pathway.