Transforming growth factor-beta family (TGFβ family)

The Transforming growth factor-beta (TGFβ) family is a large superfamily of secreted cytokines that includes TGF-beta isoforms (TGF-β1, 2, and 3), bone morphogenetic proteins (BMPs), activins, and growth differentiation factors (GDFs) (Wikipedia, 2024; NIH, 2020). These molecules are essential regulators of diverse biological processes, including cell growth, differentiation, apoptosis, and embryonic development (Frontiers, 2020). Signaling is initiated by the binding of ligands to a heterotetrameric complex of type I and type II serine/threonine kinase receptors, which subsequently activate the SMAD transcription factor pathway (PubMed, 2014). In the context of disease, the TGFβ family plays a dual role, particularly in cancer where it acts as a tumor suppressor in early stages but promotes metastasis and immune evasion in advanced stages (NIH, 2014). It is also a primary driver of tissue fibrosis across multiple organs, including the lungs, liver, and kidneys (NIH, 2021). Therapeutic targeting of the TGFβ family involves various modalities such as neutralizing antibodies, small-molecule kinase inhibitors, and bifunctional fusion proteins (Frontiers, 2020). Clinical development of these agents has been complicated by the pleiotropic nature of TGFβ signaling, leading to safety concerns like cardiotoxicity and the development of skin lesions (NIH, 2024).

Other names

Transforming growth factor-beta superfamilyTGF-beta superfamilyTGFB familyTGF-beta family

Inhibition of ligand-receptor binding via neutralizing antibodies or ligand traps, and inhibition of intracellular signaling via small-molecule kinase inhibitors targeting the type I receptor (ALK5).