BMPR2
Encyclopedia
Bone morphogenetic protein receptor type II or BMPR2 is a serine/threonine receptor kinase. It binds Bone morphogenetic proteins, members of the TGF beta superfamily of ligands. BMPs are involved in a host of cellular functions including osteogenesis, cell growth
and cell differentiation. Signaling in the BMP pathway
begins with the binding of a BMP to the type II receptor. This causes the recruitment of a BMP type I receptor, which it phosphorylates. The Type I receptor phosphorylates an R-SMAD
a transcriptional regulator.
all of the receptors exist in homodimers before ligand binding. In the case of BMP receptors only a small fraction of the receptors exist in homomeric forms before ligand
binding. Once a ligand has bound to a receptor, the amount of homomeric receptor oligomers increase, suggesting that the equilibrium
shifts towards the homodimeric form. The low affinity for ligands suggests that BMPR2 may differ in the from other type II TGF beta receptors in that the ligand may bind the type I receptor first.
An inactivating mutation in the BMPR2 gene has been linked to primary pulmonary hypertension.
BMPR2 functions (among others) to inhibit the proliferation of vascular smooth muscle so when this gene is altered vascular smooth muscle proliferates and leads to pulmonary hypertension which among other things can lead to cor pulmonale. (robbins and cotran for usmle step 1).
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
and cell differentiation. Signaling in the BMP pathway
TGF beta signaling pathway
The Transforming growth factor beta signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, apoptosis, cellular homeostasis and other cellular functions. In spite of the wide range of cellular...
begins with the binding of a BMP to the type II receptor. This causes the recruitment of a BMP type I receptor, which it phosphorylates. The Type I receptor phosphorylates an R-SMAD
R-SMAD
R-SMAD stands for receptor-regulated SMAD. Smads are transcription factors that transduce extracellular TGF-ß superfamily ligand signaling from cell membrane bound TGF-ß receptors into the nucleus where they activate transcription TGF-ß target genes...
a transcriptional regulator.
Function
Unlike the TGFβ type II receptor, which has a high affinity for TGF-β1, BMPR2 does not have a high affinity for BMP-2, BMP-7 and BMP-4, unless it is co-expressed with a type I BMP receptor. In TGF beta signalingTGF beta signaling pathway
The Transforming growth factor beta signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, apoptosis, cellular homeostasis and other cellular functions. In spite of the wide range of cellular...
all of the receptors exist in homodimers before ligand binding. In the case of BMP receptors only a small fraction of the receptors exist in homomeric forms before ligand
Ligand
In coordination chemistry, a ligand is an ion or molecule that binds to a central metal atom to form a coordination complex. The bonding between metal and ligand generally involves formal donation of one or more of the ligand's electron pairs. The nature of metal-ligand bonding can range from...
binding. Once a ligand has bound to a receptor, the amount of homomeric receptor oligomers increase, suggesting that the equilibrium
Chemical equilibrium
In a chemical reaction, chemical equilibrium is the state in which the concentrations of the reactants and products have not yet changed with time. It occurs only in reversible reactions, and not in irreversible reactions. Usually, this state results when the forward reaction proceeds at the same...
shifts towards the homodimeric form. The low affinity for ligands suggests that BMPR2 may differ in the from other type II TGF beta receptors in that the ligand may bind the type I receptor first.
An inactivating mutation in the BMPR2 gene has been linked to primary pulmonary hypertension.
External links
- GeneReviews/NCBI/NIH/UW entry on Heritable Pulmonary Arterial Hypertension
- OMIM entries on Heritable Pulmonary Arterial Hypertension
BMPR2 functions (among others) to inhibit the proliferation of vascular smooth muscle so when this gene is altered vascular smooth muscle proliferates and leads to pulmonary hypertension which among other things can lead to cor pulmonale. (robbins and cotran for usmle step 1).