ALK3

ALK3, also known as BMPR1A, is a type I serine/threonine kinase receptor in the bone morphogenetic protein (BMP) branch of the TGF-β superfamily. It functions as one of the BMP type I receptors that transduce signals from extracellular BMP ligands to intracellular signaling pathways.

The BMPR1A gene encodes the ALK3 protein, which features an extracellular ligand-binding domain, a single transmembrane helix, and an intracellular kinase domain. Upon BMP ligand binding, ALK3 forms a receptor complex with constitutively active type II BMP receptors (such as BMPR-II, ActRIIA, or ActRIIB). The type II receptor phosphorylates the GS-rich activation loop of ALK3, triggering phosphorylation of receptor-regulated Smads (Smad1, Smad5, and Smad8). These compatible Smads form a complex with the common mediator Smad4 and translocate to the nucleus to regulate transcription of BMP-responsive genes. Non-Smad signaling pathways, including MAP kinases, can also be engaged by BMP receptor activation.

ALK3 plays a critical role in development and tissue homeostasis, particularly in bone and cartilage formation, limb and craniofacial development, and dental and vascular systems. Its signaling helps govern cell differentiation and tissue remodeling in various contexts.

Clinically, germline mutations in BMPR1A are associated with juvenile polyposis syndrome, a hereditary condition characterized by multiple colorectal polyps and an elevated cancer risk. Alterations in BMP signaling involving ALK3 have also been investigated in skeletal disorders and cancer biology. Research continues into modulators of ALK3 activity for therapeutic applications in bone repair and other BMP-related conditions.