SMAD2 is a key intracellular signaling protein that plays a central role in the canonical transforming growth factor-beta (TGF-β) signaling pathway. SMAD2 is activated when TGF-β superfamily agonists bind to their receptors, leading to the phosphorylation of SMAD2. Once phosphorylated, SMAD2 forms a complex with SMAD4 and translocates into the nucleus to regulate gene expression1. SMAD2 is involved in a variety of cellular processes, including cell proliferation, differentiation, and apoptosis. It is also crucial in developmental processes, particularly in the patterning of the early embryo and the formation of the three germ layers. SMAD2-deficient mice exhibit early embryonic lethality, highlighting the essential role of SMAD2 in development. In the context of adult tissues and disease, SMAD2 has been implicated in the pathogenesis of various cancers, fibrosis, and cardiovascular diseases. It is often dysregulated in cancer, contributing to tumor progression and metastasis. In the heart, SMAD2 signaling has been shown to be important for cardiac development and responses to injury, such as myocardial infarction.
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