Transforming growth factor beta (TGF-beta) is a protein that helps control functions in cells such as differentiation and proliferation. It works as an anti-proliferative factor during early stages of oncogenesis in epithelial cells and initiate apoptosis of cancerous cells. Abnormal amounts of TGF-beta can lead to the progression of some diseases and disorders including cancer, heart disease, and Parkinson’s disease. The TGF-beta signaling pathway must start with the binding of two different receptors: type I and type II. These two protein kinases bind to each other and to the TGF-beta, and type II phosphorylates type I, initiating the signaling pathway. Multiple R-SMADs are recruited, including SARA and HGS, and mediate the pathway, ultimately leading to the activation of SMAD4, which moves into the nucleus and acts as a transcription factor and facilitates in the regulation of the expression of certain genes. Genetic variations in the TGF-beta signaling pathway have been shown to influence outcomes in certain diseases such as the Kawasaki disease.
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