BMP receptors, members of TGF-beta superfamily receptors, are two different serine/threonine kinase receptors, and mediate their signals through Smad-dependent and Smad-independent pathways. BMP receptors have been identified in humans with varying functions during processes such as embryogenesis, skeletal formation, hematopoiesis and neurogenesis. BMP signaling is activated by binding of BMP ligands to a BMP receptor complex, which consists of type II receptors (BMPR2, ActRIIa, and ActRIIb) and type I receptors (Alk1, Alk2, Alk3, and Alk6). Ligand binding induces the type II receptor to phosphorylate and activate the type I receptor. Activated type I receptors phosphorylate BMP-responsive SMAD proteins (SMADs 1, 5, and 8), which translocate together with SMAD4 into the nucleus, where they activate expression of multiple genes including those encoding hepcidin and Id-1.
The molecular signals that regulate growth and branching of the ureteric bud during formation of the renal collecting system are largely undefined. Members of the bone morphogenetic protein (BMP) family signal through the type I BMP receptor Alk3 to inhibit ureteric bud and collecting duct cell morphogenesis in vitro.
In the chick embryo, it has been shown that BMPR1B is found in precartilaginous condensations. BMPR1B is the major transducer of signals in these condensations as demonstrated in experiments using constitutively active BMPR1B receptors. BMPR1B is a more effective trasducer of GDF5 than BMPR1A. Unlike BMPR1A null mice, which die at an early embryonic stage, BMPR1B null mice are viable.
Gene BMPR2 encodes a member of the bone morphogenetic protein (BMP) receptor family of transmembrane serine/threonine kinases. The ligands of this receptor are BMPs, which are members of the TGF-beta superfamily. BMPs are involved in endochondral bone formation and embryogenesis. These proteins transduce their signals through the formation of heteromeric complexes of two different types of serine (threonine) kinase receptors: type I receptors of about 50-55 kD and type II receptors of about 70-80 kD. Type II receptors bind ligands in the absence of type I receptors, but they require their respective type I receptors for signaling, whereas type I receptors require their respective type II receptors for ligand binding. Mutations in this gene have been associated with primary pulmonary hypertension, both familial and fenfluramine-associated, and with pulmonary venoocclusive disease.