A family of proteins (mothers against decapentaplegic-related proteins, Sma- and MAD-related proteins, Smads) coded by genes that are homologous to the Drosophila gene mothers against decapentaplegic and the Caenorhabditis elegans gene Sma. The MAD-related proteins (MADRs) play critical roles in signal transduction pathways involving the TGFβ superfamily. At least eight have been identified (MADR1–7 and MADR9). Smad1 (MADR1, 465 aa) and Smad5 are activated (serine/threonine phosphorylated) by BMP receptors, Smad2 and 3 by activin and TGFβ receptors. Smad2 (MADR2, 465 aa) is important for the establishment of anterior–posterior patterning. Smad4 is important in gastrulation. Smads activated by occupied receptors form complexes with Smad4/DPC4 and move into the nucleus where they regulate gene expression and interact with the forkhead activated signal transducer. See juvenile polyposis.
Subjects: Medicine and Health.