Overview:

SMADs are essential intracellular components for the signal transduction of TGFβ family members. SMAD2 is an intracellular mediator of TGFβ family and activin type 1 receptor (1). SMAD2 mediate TGFβ signaling to regulate cell growth and differentiation. SMAD2 is released from cytoplasmic retention by TGFβ receptor-mediated phosphorylation. The phosphorylated SMAD2 then forms a heterodimeric complex with SMAD4, and this complex translocates from cytoplasm into nucleus. By interacting with DNA-binding proteins, SMAD2 complexes then positively or negatively regulate the transcription of target genes. Inactivating mutations in SMAD2 have been found in various cancers (2).

References:

1. Masayuki, F. et al: Identification and Characterization of Constitutively Active Smad2 Mutants: Evaluation of Formation of Smad Complex and Subcellular Distribution. Molecular Endocrinol. 2000; 14 (10): 1583-1591.

2. Eppert, K. et al: MADR2 maps to 18q21 and encodes a TGF-beta-regulated MAD-related protein that is functionally mutated in colorectal carcinoma. Cell. 1996; 86: 543-552.