Transforming growth factor-β (TGF-β) signals by contacting two distantly related transmem-brane serine/threonine kinases called receptors I and II. The role of these molecules in signalling has now been determined. TGF-β binds directly to receptor II, which is a constitutively active kinase. Bound TGF-β is then recognized by receptor I which is recruited into the complex and becomes phosphorylated by receptor II. Phosphorylation allows receptor I to propagate the signal to downstream substrates. This provides a mechanism by which a cytokine can generate the first step of a signalling cascade.
An overview of TGF-β receptor
Transforming growth factor beta receptors (TGF-βR) are members of TGFβ receptor family, and belong to single pass serine/threonine kinase receptors. There exist several different isoforms and they can be homo- or heterodimeric. TGF-βR can promote cell the synthesis of collagen, fibronectin, and laminin by signal transduction, and regulate normal tissue damage repair.
Major types of T GF-β receptor
According to the structure and function, TGF-β Receptors can be divided into TGF-βR1, TGF-βR2, and TGF-βR3. The ligand-binding affinity of TGF-βR1 (ALK5) and TGFβR2 is similar and they can be distinguished from each other only by peptide mapping. Both TGF-βR1 and TGF-βR2 have a high affinity for TGF-β1 and low affinity for TGF-β2.
Inhibition of TGF-β receptor
SD-208 is an alternative TGF-βRI (ALK5) inhibitor (IC 50= 48 nM), and the selectivity is >100-fold over TGF-βR2. In vitro, SD-208 can abolish the protective effects of TGF-β on the proliferation and migration of new intimal smooth muscle cells. SD-208 can also increase immunogenicity in mouse SMA-560 and human SMA-560 glioma cells, and inhibit cell growth, composition, and TGF-β induced migration and infiltration. In the mouse model of arterial allotransplantation, SD-208 can effectively reduce the formation of arterial sclerosis intimal hyperplasia.
TGF-β receptor and diseases
At present, TGF-β is believed to play a role in the TGF-βR located on the cell membrane, and the TGFβR is a high affinity binding protein of TGF-β cell membrane, which plays a pivotal role in the TGF-β signal conduction, and is the key link to determine whether the TGF-β signal conduction is normal or not. Recent studies have found that TGF-βR2 and TGF-βR3 play an important role in the development of many tumors, and are directly related to the proliferation and invasion of tumors. The expression of TGF-βR3 protein in prostate cancer and breast cancer tissues is significantly lower than that of normal tissues.