Anti-SMAD3 (human), mAb (rec.) (Phospho-T179) (SH544-IIC4)

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: Receptor-regulated SMAD (R-SMAD) that is an intracellular signal transducer and transcriptional modulator activated by TGF-beta (transforming growth factor) and activin type 1 receptor kinases. Binds the TRE element in the promoter region of many genes that are regulated by TGF-beta and, on formation of the SMAD3/SMAD4 complex, activates transcription. Also can form a SMAD3/SMAD4/JUN/FOS complex at the AP- 1/SMAD site to regulate TGF-beta-mediated transcription. Has an inhibitory effect on wound healing probably by modulating both growth and migration of primary keratinocytes and by altering the TGF-mediated chemotaxis of monocytes. This effect on wound healing appears to be hormone-sensitive. Regulator of chondrogenesis and osteogenesis and inhibits early healing of bone fractures. 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]