Anti-SMAD4 (human), mAb (rec.) (PAS7-C7)

The TGF-beta signaling pathway regulates key cell fate decisions during embryonic development and in adult homeostasis. This pathway is deregulated in many pathological conditions, including cancer, autoimmunity and fibrotic diseases. TGF-beta functions as a tumor suppressor in early tumors, inhibiting progression through the cell cycle. TGF-beta binds a heterotetrameric cell surface complex composed of type I and II serine/threonine kinase TGF-beta receptors (TGFBRI and TGFBRII). Ligand binding causes receptor phosphorylation and transmission of the signal to a class of intracellular intermediates, the receptor-regulated SMAD proteins. The SMAD family is divided into three subclasses: receptor regulated SMADs, (SMADs 1, 2, 3, 5 and 8), the common partner, (SMAD4) that functions via its interaction to the various SMADs, and the inhibitory SMADs, (SMADs 6 and 7). TGF-beta signaling pathways engage two specific receptor-regulated SMAD proteins, the SMAD2 and SMAD3. The C-terminal MH2 domains of the receptor-regulated SMADs are phosphorylated by the intracellular kinase domain of TGF-beta receptors. The receptor-regulated SMADs then interact with SMAD4 and translocate to the nucleus, where they act as transcriptional regulators. Although TGF-beta signaling engages the above three SMAD proteins, SMAD2, SMAD3 and SMAD4, there is a dominant role of SMAD3 as a mediator of both physiological, homeostatic signaling and of pathophysiological perturbed signaling in all diseases. The SMAD proteins are central nodes in the mechanisms of cross-talk between the TGF-beta pathway and other signaling pathways, including the Notch and Wnt signaling pathways. The SMAD proteins regulate multiple cellular processes, such as cell proliferation, apoptosis and differentiation. SMAD7, also known as Mothers Against Decapentaplegic homolog 7 (MADH7), inhibits selected pathways by binding directly to cell-surface receptors and preventing the activation-induced phosphorylation of other SMAD subunits. Protein function: In muscle physiology, plays a central role in the balance between atrophy and hypertrophy. When recruited by MSTN, promotes atrophy response via phosphorylated SMAD2/4. MSTN decrease causes SMAD4 release and subsequent recruitment by the BMP pathway to promote hypertrophy via phosphorylated SMAD1/5/8. Acts synergistically with SMAD1 and YY1 in bone morphogenetic protein (BMP)-mediated cardiac- specific gene expression. Binds to SMAD binding elements (SBEs) (5'- GTCT/AGAC-3') within BMP response element (BMPRE) of cardiac activating regions. Common SMAD (co-SMAD) is the coactivator and mediator of signal transduction by TGF-beta (transforming growth factor). Component of the heterotrimeric SMAD2/SMAD3-SMAD4 complex that forms in the nucleus and is required for the TGF-mediated signaling (PubMed:25514493). Promotes binding of the SMAD2/SMAD4/FAST-1 complex to DNA and provides an activation function required for SMAD1 or SMAD2 to stimulate transcription. Component of the multimeric SMAD3/SMAD4/JUN/FOS complex which forms at the AP1 promoter site, required for synergistic transcriptional activity in response to TGF- beta. May act as a tumor suppressor. Positively regulates PDPK1 kinase activity by stimulating its dissociation from the 14-3-3 protein YWHAQ which acts as a negative regulator. [The UniProt Consortium]