Transforming growth factor beta receptor type II (TGFBR2) (TGFBR2)

Transforming growth factor beta receptor type II (TGFBR2) is a transmembrane serine/threonine kinase that serves as the primary high-affinity receptor for TGF-beta ligands (TGF-beta 1, 2, and 3) [1]. Upon ligand binding, TGFBR2 forms a heteromeric complex with TGF-beta receptor type I (TGFBR1), leading to the phosphorylation and activation of SMAD2 and SMAD3, which subsequently regulate gene expression involved in cell growth, differentiation, and immune regulation [3]. In the tumor microenvironment, TGF-beta signaling often promotes tumor progression by inducing epithelial-mesenchymal transition (EMT) and suppressing the activity of immune cells like T cells and NK cells [3]. The 'dominant-negative' TGF-beta receptor type II (dnTGFBR2) is a therapeutic construct, often used in CAR-T cell engineering, that consists of the extracellular and transmembrane domains of TGFBR2 but lacks the intracellular signaling domain [2]. This truncated receptor acts as a decoy, binding TGF-beta ligands and preventing them from interacting with functional endogenous receptors, thereby shielding the therapeutic cells from TGF-beta-mediated immunosuppression and exhaustion [4]. Drugs targeting this pathway include bifunctional fusion proteins that trap TGF-beta and small molecule inhibitors of the receptor's kinase activity [5, 6]. Clinical challenges include managing systemic toxicities such as cardiovascular issues and skin lesions that can arise from broad inhibition of this pleiotropic signaling pathway [9].

Other names

TGF-beta receptor type 2TGFR-2TGF-beta-2 receptorTbetaR-IIdnTGFBR2

Competitive inhibition of TGF-beta signaling through ligand sequestration or the expression of a truncated receptor that prevents functional signaling complex formation.