Encompassing a plethora of growth, differentiation and morphogenic factors, the Transforming Growth Factor-β (TGF-β) Superfamily is comprised of signaling proteins that have been universally conserved throughout the animal kingdom and presently consists of over forty members, the likes of which include: TGF-β isoforms, bone morphogenetic proteins (BMPs), growth differentiation factors (GDFs), activins, and inhibins. Considered vital to the modulation of cell proliferation, differentiation, matrix synthesis, and apoptosis, members of the TGF-β Superfamily are fundamental to prenatal development and the postnatal growth, remodeling, and maintenance of various tissues and organs. Noted for activating Smad signaling cascades through interactions with a conserved family of cell surface serine/threonine-specific protein kinase receptors, the complexity of TGF-β signaling has been demonstrated through the additional regulation of physiological processes by TGF-β Superfamily Ligand through non-canonical pathways, and the activation of signaling molecules other than Smad proteins. Given the intricacies and significance associated with the activities of TGF-β Superfamily proteins, the impairment of proper signaling has been understandably connected to a variety of clinical indications, such as tumor cell growth, fibrosis, skeletal defects, and autoimmune disease. Therefore, understanding the regulatory mechanisms that control TGF-β signaling, as well as the identification and characterization of their molecular components, have become topics of intense investigation.
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