anti-Smad2, mAb (7A5)

The Smad family of proteins are functioning in the transmission of extracellular signals in the TGF-β signaling pathway. Binding of a TGF-β superfamily ligands to extracellular receptors triggers phosphorylation of Smad2 at a Serine-Serine-Methionine-Serine (SSMS) motif at its C-terminus. Phosphorylated Smad2 is then able to form a complex with Smad4. These complexes accumulate in the cell nucleus, where they are directly participating in the regulation of gene expression. In mammals, eight Smad proteins have been identified to date. The Smad family of proteins can be divided into three functional groups: the receptor-activated Smads (R-Smads), common mediator Smads (Co-Smads), and the inhibitory Smads (I-Smads). The R-Smads are directly phosphorylated by the activated type I receptors on their C-terminal Ser-Ser-X-Ser (SSXS) motif and include Smad1, Smad2, Smad3, Smad5, and Smad8. Smad2 and Smad3 are phosphorylated in response to TGF-β and activin, whereas Smad1, Smad5, and Smad8 are phosphorylated in response to BMP (Bone Morphogenetic Protein). This C-terminal phosphorylation allows R-Smad binding to Co-Smad, Smad4, and translocation to the nucleus where they regulate TGF-β target genes. Smad6 and Smad7 belong to the I-Smad which bind to the type I receptor or Smad4 and block their interaction with R-Smads. The Smads share sequence similarities, most notably in the N-terminal and carboxy-terminal regions, referred to as the MH1 (Mad Homology 1) and MH2 domains respectively. Smad2 and Smad3 have 66% amino acid sequence identity between their MH1 domains and 96% amino acid sequence identity between their MH2 domains. Transcriptional modulator activated by TGF-β and activin type 1 receptor kinase. SMAD2 is a receptor-regulated SMAD (R-SMAD). May act as a tumor suppressor in colorectal carcinoma.