Transforming growth factor beta 3: The TGFB3 gene provides instructions for producing a protein called transforming growth factor beta-3 (TGFβ-3).
The TGFB3 gene provides instructions for producing a protein called transforming growth factor beta-3 (TGFβ-3). This protein is found throughout the body and is required for development before birth and throughout life. To carry out its functions, TGFβ-3 attaches (binds) to receptor proteins on the surface of cells. This binding triggers the transmission of signals within the cell, controlling various cellular activities. As part of a signaling pathway, called the TGF-β pathway, the TGFβ-3 protein helps control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (motility), and controlled cell death (apoptosis). Because the TGFβ-3 protein keeps cells from growing and dividing too rapidly or in an uncontrolled way, it can suppress the formation of tumors.
The TGFβ-3 protein is especially abundant in tissues that develop into the muscles used for movement (skeletal muscles), and plays a key role in their development. The protein is also involved in the formation of blood vessels, regulation of bone growth, wound healing, and immune system function.
At least 11 mutations in the TGFB3 gene have been found to cause Loeys-Dietz syndrome type V. This disorder affects connective tissue, which gives structure and support to blood vessels, the skeleton, and many other parts of the body. Loeys-Dietz syndrome type V is characterized by blood vessel abnormalities, heart defects, and skeletal deformities. The TGFB3 gene mutations that cause this condition lead to the production of a TGFβ-3 protein with little or no function. As a result, the protein cannot bind to its receptors. Although the TGFβ-3 protein and its receptors are not bound, TGF-β pathway signaling occurs at an even greater intensity than normal. Researchers speculate that the activity of other proteins in this signaling pathway is increased to compensate for the reduction in TGFβ-3 activity; however, the exact mechanism responsible for the increase in signaling is unclear. The overactive signaling pathway disrupts development of connective tissue and various body systems and leads to the signs and symptoms of Loeys-Dietz syndrome type V.