Activin receptor type-1B (ACVR1B) (ACVR1B)

Activin receptor type-1B (ACVR1B), also known as ALK-4, is a type I transmembrane serine/threonine kinase receptor that plays a pivotal role in the TGF-beta/Activin signaling pathway (UniProt P36896). It functions by forming a heteromeric complex with type II activin receptors upon ligand binding (such as Activin A, B, or Nodal), leading to the phosphorylation and activation of ACVR1B. Once active, it phosphorylates the intracellular signaling proteins SMAD2 and SMAD3, which then move to the nucleus to regulate gene expression related to cell growth, differentiation, and development (PubMed: 21151574). In clinical contexts, ACVR1B is notably involved in oncology; it acts as a tumor suppressor in pancreatic and colorectal cancers, where mutations often lead to loss of function (PubMed: 11441003). However, in other scenarios, such as organ fibrosis or certain advanced cancers, its signaling can promote disease progression. Therapeutic development focuses on small molecule inhibitors that target the kinase domain of ACVR1B, frequently in conjunction with ALK-5 (TGFBR1) inhibition, to treat various solid tumors and fibrotic conditions.

Other names

ALK-4ALK4ACTR-IBSKR2Serine/threonine-protein kinase receptor R3

Small molecule inhibition of the intracellular kinase domain, preventing the phosphorylation of SMAD2/3 and subsequent downstream gene transcription.