Transforming growth factor-beta superfamily receptors (TGF-β/BMP receptors)

The Transforming growth factor-beta (TGF-β) and Bone morphogenetic protein (BMP) receptors constitute a major family of cell-surface serine/threonine kinase receptors that mediate signals for a diverse range of cellular processes, including cell proliferation, differentiation, and apoptosis (UniProt, P36897; P37173). These receptors typically function as heteromeric complexes where a Type II receptor phosphorylates and activates a Type I receptor (also known as Activin receptor-like kinases or ALKs) upon ligand binding, subsequently triggering the SMAD signaling cascade (PubMed, 29222235). In clinical contexts, dysregulation of these pathways is heavily implicated in the progression of various cancers, where TGF-β can promote epithelial-mesenchymal transition (EMT) and immune evasion, as well as in fibrotic diseases and cardiovascular conditions like pulmonary arterial hypertension (PubMed, 30655606). Therapeutic interventions targeting these receptors include small-molecule inhibitors of the Type I receptor kinase (e.g., galunisertib), monoclonal antibodies against the ligands or receptors (e.g., fresolimumab), and ligand traps that sequester circulating TGF-β or BMP ligands (e.g., sotatercept) (DrugBank, DB12735; DB11627). Despite their therapeutic potential, targeting this superfamily is complicated by their pleiotropic nature, leading to safety concerns such as cardiovascular toxicity and the development of benign skin lesions (PubMed, 25135934).

Other names

TGF-beta receptorsBMP receptorsActivin receptorsALK receptorsSerine/threonine-protein kinase receptorsTGFBRBMPR

Inhibition of Type I receptor (ALK) kinase activity, sequestration of TGF-beta/BMP ligands via decoy receptors (ligand traps), or competitive binding to the receptor extracellular domain by monoclonal antibodies.