SMAD signalling comprises an intracellular pathway regulating a range of cellular processes, particularly the control of gene expression during development, tissue homeostasis, and disease. This signalling pathway is mediated by a family of transcription factor proteins, SMADs, which transduce signals from ligands such as transforming growth factor-beta (TGF-β) and bone morphogenetic proteins (BMPs). Receptor-Regulated SMADs (R-SMADs), such as SMAD2 and SMAD3, are activated by TGF-β family ligands, such as TGF-β1 and TGF-β2. The TGF-β ligand binds to its cell surface receptor, which consists of two serine/threonine kinase (type I and type II) receptors. TGF-β initially binds to the Type II receptor which becomes activated and phosphorylates the Type I receptor. The activated Type I receptor, also a serine/threonine kinase, then phosphorylates R-SMADs, inducing a conformational change and exposing a hydrophobic region known as the MH2 domain, allowing complexing to the common mediator SMAD4 (Co-SMAD). Common SMAD (Co-SMAD), SMAD4, forms complexes with R-SMADs upon ligand activation that mediate nuclear translocation and binding to target genes. SMAD4, also known as DPC4 (Deleted in Pancreatic Cancer locus 4), is a tumour suppressor gene essential for various developmental processes and frequently mutated in cancer. Once activated, SMAD complexes translocate into the nucleus, where they regulate gene expression. In the nucleus, SMAD complexes bind to specific DNA sequences in the promoters of target genes, often referred to as SMAD-binding elements (SBEs). This binding results in the regulation of gene expression, either by activating or repressing target genes, depending on the context. SMAD-regulated genes are primarily involved in regulating processes including cell growth, differentiation, and tissue repair. SMAD complexes can recruit coactivator or corepressor proteins to modulate gene transcription further. For example, CBP/p300 (CREB-binding protein/EP300) and p300/CBP-associated factor (PCAF) are coactivators that possess histone acetyltransferase (HAT) activity, allowing them to acetylate histones and promote chromatin remodelling. This facilitates the binding of p-SMAD complexes to target gene promoters, enhancing transcriptional activation. Inhibitory SMADs (I-SMADs) such as SMAD6 and SMAD7 function as negative regulators of SMAD signaling. They inhibit the activation of R-SMADs by competing for binding to the type I receptor kinase domain. SMAD6 primarily regulates BMP signalling, whilst SMAD7 modulates TGF-β and other pathways. These I-SMADs play roles in maintaining pathway homeostasis and preventing excessive signalling. SMAD signalling is essential for embryonic development. BMPs and TGF-β family members control processes such as dorsoventral patterning, neural tube closure, limb development, and organogenesis. SMAD signaling also plays a role in tissue homeostasis and repair. For example, TGF-β is involved in tissue remodelling, wound healing, and fibrosis with BMPs critical for bone and cartilage formation and regeneration. SMAD signalling can also regulate immune responses. TGF-β for example has immunosuppressive effects, influencing immune cell differentiation, proliferation, and function. Finally, dysregulation of SMAD signaling is frequently observed in cancer. Mutations or aberrant activation of SMAD proteins can lead to uncontrolled cell proliferation, invasion, and metastasis. In hepatocellular carcinoma (HCC), SMAD2 and SMAD3, which are normally involved in TGF-β signalling, can acquire mutations that render them constitutively active. We provide a wide product range of research reagents for studying SMADs, including c-Jun antibodies, Smad4 antibodies, Smad3 antibodies, c-Jun ELISA Kits, and Smad3 ELISA Kits. Explore our full SMADs product range below and discover more, for less.