Transforming growth factor beta 1 and receptors (TGF-β1/TGFBR)

Transforming growth factor beta 1 (TGF-β1) is a multifunctional cytokine that regulates cell growth, differentiation, and immune function by signaling through a complex of transmembrane serine/threonine kinase receptors, primarily TGFBR1 (ALK5) and TGFBR2 [UniProt: P01137, P36897]. Upon TGF-β1 binding, TGFBR2 phosphorylates and activates TGFBR1, which subsequently phosphorylates SMAD2 and SMAD3 to modulate the transcription of target genes involved in the epithelial-mesenchymal transition (EMT) and extracellular matrix synthesis [PubMed: 28648118]. In oncology, the TGF-β pathway exhibits a TGF-β paradox, where it functions as a tumor suppressor in early-stage disease but promotes progression, metastasis, and immune evasion in advanced stages [PubMed: 30612166]. It is also a master regulator of fibrosis, contributing to the pathogenesis of chronic kidney disease, pulmonary fibrosis, and cirrhosis [PubMed: 22329236]. Pharmacological interventions include neutralizing antibodies like fresolimumab and small-molecule kinase inhibitors like galunisertib, though clinical use is often limited by side effects such as keratoacanthomas and potential cardiovascular toxicity [PubMed: 26025111].

Other names

TGFB1TGF-beta 1TGFBR1TGFBR2ALK5TGF-beta receptor type ITGF-beta receptor type IITGF-beta receptor type IIIBetaglycanSKR5

Inhibition of TGF-β ligand binding to its receptors or inhibition of the intracellular serine/threonine kinase activity of TGFBR1 to block downstream SMAD-dependent and SMAD-independent signaling pathways.