About TGFBR / TGFB Receptor:
TGFBR or transforming growth factor beta receptors belong to the TGF beta receptor family. They exist in a variety of forms and have more ligands than receptors, suggesting that there are multiple ligand-receptor interactions.
TGFBR Function
The purpose of TGFBR is to stimulate the body to grow new tissues. It is found all over the body, including in bone, liver, brain, heart, kidneys, and testes. Researchers also believe that it is a signaling molecule too. There is evidence that it acts as a cytokine for the pancreas, sending signals to the rest of the body for how much energy is available in the bloodstream.
While TGFBR is beneficial in small quantities (like most growth factors), it can be damaging when administered in high doses. Research suggests, for instance, that high levels of TGF factor beta can induce fibrosis of the kidneys and pancreas, leading to both kidney disease and diabetes.
Recently, researchers and drug companies have been investigating ways to manipulate TGBR to address these diseases. The idea at present is to use TGFBR antagonists to reduce levels of the enzyme in tissues throughout the body, counteracting some of the adverse effects induced by excessively high levels. Experiments to date suggest that there may be a way to reverse renal fibrosis and restore healthy tissue function.
Other research suggests that finding ways to inhibit TGFBR may also help to treat cancer. Samples from cancerous tissues show overexpression of TGFBR - presumably an adaptation by the tumor to accelerate its growth. Higher levels of TGFBR lead to faster cell division and growth and encourages the formation of more aggressive tumors that grow and spread faster. Inhibiting the TGFBR signaling pathways, therefore, could be a way to combat cancer, particularly at the end-stage of the disease.
TGFB Receptor Structure
TGFBR has been categorized into a variety of distinct isoforms that are both homo and heterodimeric.
Researchers classify three TGF beta factor superfamily receptors, which all have different structures and functions.
TGF beta receptor 1, also sometimes called ALK5 and TGF beta receptor 2, both have similar ligand-binding preferences. The differences between them are subtle and only visible through a careful process of peptide mapping. Both of them have a high affinity for TGF-beta-1 and a low preference for TGF-beta-2.
TGF beta receptor 3 likes to bind to homodimeric versions of TFG-beta-1 and TGF-beta-2. It will also link with the heterodimer TGF-beta-1.2 and TGF-beta-3.
TGFBR Mechanisms
The majority of TGFBRs resides in cells. However, following AKT activation in response to insulin or other growth factors, it soon makes its way to the surface to increase affinity for TGF-beta. Interestingly, research indicates that TGF-beta induces the translocation of its own receptors to the cell surface, enhancing the mechanism of action. They also discovered that TGF-beta-induced increases in receptor populations at the cell surface amplified the work of SMAD family members,
The role of bone morphogenic protein 4 is essential too. It increases AKT activation, which, in turn, increases the TGFBR levels at the cell surface. This finding provides a context for TGF-beta signaling during development.