Bone morphogenetic protein receptor type 2 (BMPR2) (BMPR2)

Bone morphogenetic protein receptor type 2 (BMPR2) is a transmembrane serine/threonine kinase receptor belonging to the transforming growth factor-beta (TGF-beta) superfamily [16, 24]. It is essential for vascular homeostasis, regulating the balance between cell proliferation and apoptosis in pulmonary artery endothelial and smooth muscle cells [19, 21]. Mutations in the BMPR2 gene are the primary cause of heritable pulmonary arterial hypertension (PAH) and are found in approximately 20% of idiopathic cases, leading to uncontrolled vascular remodeling [18, 22]. Beyond PAH, BMPR2 is involved in embryogenesis, bone formation, and the progression of certain cancers like colorectal and prostate cancer [12, 23]. Therapeutic strategies focus on restoring the BMPR2 signaling pathway, which is often downregulated in disease states [4, 10]. For example, sotatercept acts as a ligand trap to sequester activins, thereby rebalancing the TGF-beta/BMP axis [2, 14]. Other approaches include using low-dose tacrolimus to activate downstream SMAD signaling or experimental agents to increase receptor expression [1, 3, 11].

Other names

BMPR2BMPR-IIPPH1BMR2BRK-3T-ALKBMPR3POVD1

Ligand trapping of activins and growth differentiation factors to restore signaling balance; direct activation of downstream SMAD signaling; enhancement of receptor expression; and nonsense mutation read-through [2, 4, 10, 25].