Bone morphogenetic protein receptor type I and type II (BMPR-I and BMPR-II (or collectively BMPRs); type I receptors are often referred to as ALK1–ALK7, with BMP signaling using ALK2 (ACVR1), ALK3 (BMPR-IA), and ALK6 (BMPR-IB). Type II is commonly called BMPR2[2][4])

Molecular Classification

Receptor, Serine/threonine kinase receptor, Transmembrane protein, TGF-β superfamily receptor

Other Names

BMPR-I (type I receptor, including BMPR-IA/ALK3, BMPR-IB/ALK6, ACVRL1/ALK1, ACVR1/ALK2), BMPR-II (type II receptor), ALK1, ALK2, ALK3, ALK6 (type I subtypes), Activin receptor-like kinase (ALK), ACVRL1 (for ALK1), ACVR1 (for ALK2), BMPR2 (for type II), TGF-β superfamily receptor

Disease Roles

Cancer (e.g., juvenile polyposis syndrome)Pulmonary arterial hypertension (PAH) (mutations in BMPR2)Fibrodysplasia ossificans progressiva (FOP) (mutations in ACVR1/ALK2)

Bone morphogenetic protein receptor type I and type II Overview

Bone morphogenetic protein receptor type I and type II refer collectively to a signaling system composed of serine/threonine kinase transmembrane receptors that are part of the TGF-β receptor superfamily. These receptors form heteromeric tetrameric complexes (two type I and two type II receptors) upon binding to BMP ligands, which triggers intracellular signaling via phosphorylation of SMAD transcription factors and modulates cell differentiation, proliferation, and development. Mutations in these receptors cause diverse diseases including pulmonary arterial hypertension, certain cancers, and abnormal bone formation syndromes, making them attractive but challenging therapeutic targets[2][4][5]

Mechanism of Action

Kinase inhibition (blocking BMPR-mediated phosphorylation; e.g., inhibitor drugs); Ligand binding (recombinant BMPs bind and activate receptors); Signal transduction modulation (SMAD phosphorylation, affecting gene expression)

Biological Functions

Signal transduction (via SMAD and non-SMAD pathways)

Cell proliferation

Differentiation (especially osteoblasts, cartilage, neuronal)

Embryogenesis (tissue patterning, organogenesis)

Homeostasis (adult tissue regulation)

Bone and cartilage formation

Vascular development

Osteogenesis

Disease Associations

Cancer (e.g., juvenile polyposis syndrome)

Pulmonary arterial hypertension (PAH) (mutations in BMPR2)

Fibrodysplasia ossificans progressiva (FOP) (mutations in ACVR1/ALK2)

Diffuse intrinsic pontine glioma (DIPG) (mutations in ACVR1/ALK2)

Hereditary hemorrhagic telangiectasia (Endoglin, ACVRL1/ALK1)

Juvenile hemochromatosis (RGMc)

Vascular, skeletal, and developmental disorders

Safety Considerations

On-target toxicity (disrupted bone or vascular homeostasis)
Developmental effects (since BMP receptors are crucial in embryogenesis)
Risk of ectopic bone formation (seen in FOP)
Vascular complications (e.g., PAH due to loss of BMPR2 function)

Interacting Drugs

Kinase inhibitors (small molecules targeting BMPR kinase activity)

Recombinant BMP ligands (activators)

Associated Biomarkers

Biomarker
BMPR2 mutation status (for PAH patient selection)
ALK2/ACVR1 mutation status (for FOP and DIPG)
Smad phosphorylation/activity levels (for pathway activation)