BMP receptor-1A, soluble

The extracellular domain of human BMPR-IA was fused with a carboxy-terminal 6X histidine-tag. The monomeric glycoprotein was expressed in baculovirus infected insect cells. Cellular responses to bone morphogenetic proteins (BMPs) have been shown to be mediated by the formation of hetero-oligomeric complexes of the type I and type II serine/threonine kinase receptors. BMP receptor 1A (BMPR-1A), also known as activin receptor-like kinase (ALK)-3, is a one of seven known type I serine/threonine kinases that are required for the signal transduction of TGF-b family cytokines. In contrast to the TGF-b receptor system in which the type I receptor does not bind TGF-b in the absence of the type II receptor, type I receptors involved in BMP signaling (including BMPR-IA, BMPR-IB/ALK-6, and ActR-I/ALK-2) can independently bind the various BMP family proteins in the absence of type II receptors. Recombinant soluble BMPR-IA binds BMP-2 and -4 with high-affinity in solution and is a potent BMP-2/4 antagonist in vitro. BMPR-IA is ubiquitously expressed during embryogenesis. In adult tissues, BMPR-IA mRNA is also widely distributed; with the highest expression levels found in skeletal muscle. The extracellular domain of BMPR-IA shares little amino acid sequence identity with the other mammalian ALK type I receptor kinases, but the cysteine residues are conserved. Human and mouse BMPR-IA are highly conserved and share 98% sequence identity.