TGFBR2

What is TGFBR2 protein?

TGFBR2 gene (transforming growth factor beta receptor 2) is a protein coding gene which situated on the short arm of chromosome 3 at locus 3p24. The protein encoded by this gene is a transmembrane protein that has a protein kinase domain, forms a heterodimeric complex with TGF-beta receptor type-1, and binds TGF-beta. This receptor/ligand complex phosphorylates proteins, which then enter the nucleus and regulate the transcription of genes related to cell proliferation, cell cycle arrest, wound healing, immunosuppression, and tumorigenesis. The TGFBR2 protein is consisted of 567 amino acids and TGFBR2 molecular weight is approximately 64.6 kDa.

What is the function of TGFBR2 protein?

TGFBR2, or transforming growth factor β receptor type II, is a transmembrane protein that plays a critical role in regulating cell proliferation, differentiation, migration, apoptosis, and extracellular matrix production. As a key component of TGF-β superfamily signaling, TGFBR2 activates its intrinsic tyrosine kinase activity by binding to TGF-β ligands, thereby triggering intracellular signaling pathways, such as the Smad pathway, to regulate gene expression and cell behavior. Dysfunction of TGFBR2 is associated with the development of a variety of diseases, including fibrotic diseases, cardiovascular diseases, and certain cancers.

TGFBR2 related signaling pathway

The TGFBR2 protein is a key component of the TGF-β signaling pathway. When it binds to TGF-β ligands, it activates a range of intracellular signaling processes, including classical and non-classical Smad independent pathways. In the SMAD-dependent pathway, TGFBR2 activates Smad2 and Smad3, which are phosphorylated and bind to Smad4 to form complexes that migrate to the nucleus and regulate the expression of multiple genes. The non-classical pathway involves MAPK, PI3K/Akt and Rho GTPase signaling pathways, which affect cell proliferation, differentiation, migration and apoptosis.

Fig1. TGF-β canonical and noncanonical signaling. (Alexandra Vander Ark, 2018)

TGFBR2 related diseases

The protein encoded by the TGFBR2 gene is a key component of the transforming growth factor β (TGF-β) signaling pathway, and its abnormal function has been associated with a variety of diseases. Mutations in the TGFBR2 gene are associated with Marfan syndrome type 2 (MFS2), an inherited connective tissue disease characterized by abnormalities of the cardiovascular system, such as aortic aneurysms and aortic dissection. In addition, abnormalities in the TGFBR2 gene have been associated with Lowy-Dietz syndrome (LDS), a disorder characterized by aortic aneurysms, staphylostaphyloplasty, and widening of the eye distance. In the field of oncology, decreased expression of TGFBR2 is associated with the progression of prostate cancer, while in lung cancer, high activity of TGFBR2 may be associated with tumor aggressiveness and resistance to immunotherapy. In cervical cancer, abnormal expression of TGFBR2 is associated with tumor development and chemotherapy sensitivity.

Bioapplications of TGFBR2

rhTGFBR2 can be used for drug screening and activity evaluation in the development of targeted therapeutics targeting the TGF-β signaling pathway, especially in the development of anti-tumor and fibrosis therapeutics. The change of rhTGFBR2 expression level may be related to the occurrence and development of some diseases, so it may be used as a biomarker for the diagnosis and prognosis assessment of diseases. rhTGFBR2 or its related genes may be used in gene therapy strategies, particularly in the treatment of diseases caused by abnormalities in the TGF-β signaling pathway. During tissue repair and regeneration, rhTGFBR2 may promote tissue healing and functional recovery by regulating extracellular matrix production and remodeling.

Case Study 1: Zhaoping Qin, 2018

In youthful skin, fibroblasts' attachment to the collagen-rich extracellular matrix (ECM) via integrins supports collagen production and skin strength. Aging leads to ECM fragmentation and reduced fibroblast attachment, decreasing collagen and causing skin to thin and weaken. Disrupting the actin cytoskeleton in fibroblasts inhibits the TGF-β pathway, crucial for collagen synthesis, by reducing the TGF-β type II receptor (TβRII) and downstream signaling. This inhibition is reversible, and cytoskeleton reassembly restores collagen production. Additionally, the cytoskeleton's impact on TβRII is through microRNA 21, which suppresses its expression.

Fig1. Fibroblasts were transfected with TβRII expression vector, and 48 h later treated with Lat-A.

Fig2. TβRII protein levels.

Case Study 2: Gang Li, 2017

This study explored the role of miR-9-5p in non-small cell lung cancers (NSCLCs), focusing on its potential targeting of TGFBR2. Researchers found miR-9-5p to be upregulated in NSCLC tissues compared to normal lung tissues. Overexpression of miR-9-5p enhanced cellular proliferation, metastasis, and invasion in NSCLC cells, while its inhibition had the opposite effect. Luciferase reporter assays confirmed TGFBR2 as a direct target of miR-9-5p. Knocking down TGFBR2 negated the suppressive effects of miR-9-5p on p-smad2 and p-smad3, suggesting that miR-9-5p promotes NSCLC cell aggressiveness by targeting TGFBR2.

Fig3. The expressions of TGFBR2, P-smad2, smad2, p-smad3 and smad3 were analyzed by western-blot.

Fig4. TGFBR2 expressions in BEAS-2B, A549, SK-MES-1 and H1299 cell lines.

TGFBR2 has several biochemical functions, for example, ATP binding,SMAD binding,glycosaminoglycan binding. Some of the functions are cooperated with other proteins, some of the functions could acted by TGFBR2 itself. We selected most functions TGFBR2 had, and list some proteins which have the same functions with TGFBR2. You can find most of the proteins on our site.

TGFBR2 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with TGFBR2 here. Most of them are supplied by our site. Hope this information will be useful for your research of TGFBR2.

TGFB1;TGFB3;SCUBE3