Background:
SMAD5 is a member of the Mothers Against Dpp (MAD)-related family of proteins. It is a receptor-regulated SMAD (R-SMAD), and acts as an intracellular signal transducer for the transforming growth factor beta superfamily. SMAD5 is activated through serine phosphorylation by BMP (bone morphogenetic proteins) type 1 receptor kinase. It is cytoplasmic in the absence of its ligand and migrates into the nucleus upon phosphorylation and complex formation with SMAD4. Here the SMAD5/SMAD4 complex stimulates the transcription of target genes.