TGF-β Receptor

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.

1099644-42-4
ITD-1
1099644-42-4
B0084-462343
EW-7197
1352608-82-2
356559-20-1
SB525334
356559-20-1
396129-53-6
LY364947
396129-53-6
B0084-068993
Repsox
446859-33-2
452342-67-5
GW788388
452342-67-5
607737-87-1
A-77-01
607737-87-1
B0084-272365
SD-208
627536-09-8
B0084-307752
Galunisertib
700874-72-2
B0084-155117
A83-01
909910-43-6

Background


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.