The BMPR1A gene spans 27 exons and encodes a 532-amino acid protein. It forms heterotetrameric complexes with BMPR2 upon ligand binding, initiating downstream signaling .
BMPR1A activates SMAD1/5/8 proteins, which complex with SMAD4 to regulate transcription of genes involved in:
Canonical Pathway: BMPR1A phosphorylates SMADs, enabling nuclear translocation for gene regulation .
Non-Canonical Pathways: Modulates MAPK and PI3K/AKT pathways in tissue-specific contexts .
Breast/Colon Carcinoma: Somatic mutations correlate with tumor progression .
Leukemia: Altered BMPR1A expression linked to B-lymphoblastic leukemia .
Expression System: CHO cells yield glycosylated, bioactive homodimers .
Stability: Lyophilized form stable at -18°C; reconstituted protein usable for 7 days at 4°C .
Bone Regeneration: Enhances osteoblast extracellular matrix deposition .
Neural Repair: Palmitoylation at C180 regulates oligodendrocyte differentiation .
Cancer Therapy: Inhibitors like LDN-193189 block BMPR1A in preclinical models .
Myeloid BMPR1A in Cancer
Germinal Center Regulation
Lung Development
Palmitoylation: At Cys180 directs receptor trafficking; mutations reduce surface expression in neural stem cells .
Phosphorylation: Activates kinase domain for SMAD recruitment .
Inhibitor | Target | Clinical Stage | Reference |
---|---|---|---|
LDN-193189 | BMPR1A/ALK2 | Preclinical | |
ML347 | ALK3 (BMPR1A) | Preclinical | |
DMH1 | BMPR1A/ALK2 | Preclinical |
Bone morphogenetic protein (BMP) receptors are transmembrane serine/threonine kinases. This family includes type I receptors BMPR1A and BMPR1B, and the type II receptor BMPR2. These receptors are structurally similar to ACVR1 and ACVR2 receptors. Ligands for these receptors belong to the TGF-beta superfamily. TGF-betas initiate signal transduction by forming heteromeric complexes with two different types of serine/threonine kinase receptors: type I receptors (approximately 50-55 kDa) and type II receptors (approximately 70-80 kDa). Type II receptors can bind ligands independently of type I receptors. However, they require type I receptors for signaling. Conversely, type I receptors rely on type II receptors for ligand binding.
BMPR-1A, BMP-R1A, BMPR1A, BMR1A, CD292, CD-292, Serine/threonine-protein kinase receptor R5, SKR5, ALK-3, ACVRLK3, EC 2.7.11.30, CD292 antigen.
Bone Morphogenetic Protein Receptor Type IA (BMPR1A), also known as Activin Receptor-Like Kinase 3 (ALK3), is a crucial component of the transforming growth factor-beta (TGF-β) superfamily. This receptor is a transmembrane serine/threonine kinase that plays a significant role in various biological processes, including embryonic development, bone formation, and cellular differentiation .
BMPR1A is a type I receptor that forms a heteromeric complex with type II receptors upon ligand binding. This complex is essential for the signal transduction of bone morphogenetic proteins (BMPs), which are key regulators of bone and cartilage development . The receptor’s structure includes an extracellular ligand-binding domain, a single transmembrane domain, and an intracellular serine/threonine kinase domain .
BMPR1A is involved in numerous developmental processes. It is crucial for dorso-ventral patterning, neural crest development, and organogenesis, including the development of the heart, kidneys, and thymus . Additionally, BMPR1A plays a role in chondrogenesis, skeletal development, and hematopoiesis .
Recombinant BMPR1A is produced using recombinant DNA technology, which involves inserting the BMPR1A gene into an expression vector and introducing it into a host cell, such as E. coli or mammalian cells. The host cells then produce the BMPR1A protein, which can be purified and used for various research and therapeutic applications .