TGFBR1

Case study 1: David A Monteiro, 2021

Bone is a dynamic tissue that constantly adapts to changing mechanical demands. The transforming growth factor beta (TGFβ) signaling pathway plays several important roles in maintaining skeletal homeostasis by both coupling the bone-forming and bone-resorbing activities of osteoblasts and osteoclasts and by playing a causal role in the anabolic response of bone to applied loads. However, the extent to which the TGFβ signaling pathway in osteocytes is directly regulated by fluid shear stress (FSS) is unknown.

To investigate the effects of FSS on TGFβ signaling in osteocytes, the researchers stimulated osteocytic OCY454 cells cultured within a microfluidic platform with FSS. Relative to treatment with TGFβ, FSS induced a larger increase in levels of pSmad2/3 and Serpine1 that persisted even in the presence of a TGFβ receptor type I inhibitor. The results show that FSS stimulation rapidly induces phosphorylation of multiple TGFβ family R-Smads by stimulating multimerization and concurrently activating several TGFβ and BMP type I receptors, in a manner that requires the activity of the corresponding ligand.

Fig1. Representative images of Smad2/3 nuclear localization in control cells or following 30-minute treatments with FSS (0.1 Pa) or TGFβ (5 ng/mL).

Fig2. Representative western analysis of Smad phosphorylation in control cells and cells pretreated (60 minutes) with vehicle or an inhibitor of a subset of TGFβ type I receptors (SB-431542, ALK4/5/7 inhibitor.

Case study 2: Seong Ji Park, 2016

Transforming growth factor-β1 (TGF-β1) promotes tumor metastasis by inducing an epithelial-to-mesenchymal transition (EMT) in cancer cells. In this study, the researchers investigated the effects of BIX02189 and XMD8-92, pharmacologic inhibitors of the MEK5 [mitogen-activated protein kinase/extracellular-signal-regulated kinase (ERK)5] signaling pathway, on the EMT and migration of cancer cells induced by TGF-β1. In human A549 lung cancer cells, TGF-β1-induced EMT, cell motility, and expression of matrix metalloproteinase-2 were completely inhibited by BIX02189, but not by XMD8-92 or small interference RNAs specific to MEK5 and ERK5. Molecular docking simulation and kinase assays revealed that BIX02189 binds directly to the ATP-binding site of the TGF-β receptor type I (TβRI) and suppresses its kinase activity. Finally, the anti-metastatic effect of BIX02189 was validated in a TβRI-derived A549 xenograft mouse model.

Fig3. A549 cells were pretreated with BIX02189 (upper panel) or XMD8-92 (lower panel) at the indicated concentrations for 30 min and then stimulated with TGF-β1 (5 ng/ml) for 36 h in serum-free medium.

Fig4. A549 cells were pretreated with BIX02189 (5 μM) for 30 min and then stimulated with TGF-β1 (5 ng/ml) for an additional 30 min.

Fig1. G–CSF–PK2-STAT3 signaling circuit in neutrophils. (Hong-Lian Wang, 2022)

Fig2. TGF-β signaling pathway. In the Smad signaling pathway, the latent TGF-β is activated by integrins and becomes active TGF-β. (Junmin Wang, 2021)

TGFBR1 involved in several pathways and played different roles in them. We selected most pathways TGFBR1 participated on our site, such as MAPK signaling pathway, Cytokine-cytokine receptor interaction, FoxO signaling pathway, which may be useful for your reference. Also, other proteins which involved in the same pathway with TGFBR1 were listed below. Creative BioMart supplied nearly all the proteins listed, you can search them on our site.

TGFBR1 has several biochemical functions, for example, ATP binding, I-SMAD binding, SMAD binding. Some of the functions are cooperated with other proteins, some of the functions could acted by TGFBR1 itself. We selected most functions TGFBR1 had, and list some proteins which have the same functions with TGFBR1. You can find most of the proteins on our site.

TGFBR1 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 TGFBR1 here. Most of them are supplied by our site. Hope this information will be useful for your research of TGFBR1.

q99ib8-pro_0000045599; TGFB3; FKBP1A; YWHAZ; TGFB1; Rnf5