Transforming growth factor-beta receptor family (TGFBR family)

The Transforming growth factor-beta (TGF-β) receptor family consists of single-pass transmembrane serine/threonine kinases that play a pivotal role in regulating diverse cellular processes, including growth, differentiation, and immune homeostasis [1][2]. Upon binding of TGF-β ligands, the Type II receptor (TGFBR2) phosphorylates and activates the Type I receptor (TGFBR1/ALK5), which then initiates intracellular signaling through the SMAD protein family [3]. In oncology, this pathway is often hijacked to promote epithelial-mesenchymal transition (EMT), metastasis, and immune evasion within the tumor microenvironment [4]. Beyond cancer, dysregulation of TGF-β receptors is a primary driver of fibrotic diseases in the lungs, liver, and kidneys, as well as various cardiovascular conditions like Loeys-Dietz syndrome [5]. Therapeutic strategies targeting this family include small molecule kinase inhibitors, monoclonal antibodies, and ligand traps [6]. However, the pleiotropic nature of TGF-β signaling presents significant challenges, as systemic inhibition can lead to adverse effects such as cardiotoxicity and the development of skin lesions [7]. Current research focuses on developing more selective inhibitors and combination therapies to mitigate these risks while maximizing therapeutic efficacy in refractory tumors [8].

Other names

TGF-beta receptorsTGFBRSerine/threonine-protein kinase receptorsTransforming growth factor beta receptors

Small molecule inhibition of the intracellular serine/threonine kinase domain (primarily TGFBR1), monoclonal antibody-mediated blockade of ligand-receptor binding, and bifunctional fusion proteins that sequester ligands while targeting other pathways.