BMPR2 Antibodies

Bone morphogenetic protein receptor type-2 (BMPR2)

On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then bind and activate SMAD transcriptional regulators.

Binds to BMP7, BMP2 and, less efficiently, BMP4. Binding is weak but improved by the presence of type I receptors for BMPs.

Gene Information

Human
Gene Name:	BMPR2
Uniprot:	Q13873
Entrez:	659

Family

Belongs to:
protein kinase superfamily

Alternative Names

BMP type II receptor; BMP type-2 receptor; BMPR2; BMPR-2; BMPR3; BMPRII; BMPR-II; BMPR-IIprimary pulmonary hypertension 1; Bone morphogenetic protein receptor type II; bone morphogenetic protein receptor type-2; bone morphogenetic protein receptor, type II (serine/threonine kinase); BRK-3; EC 2.7.11; EC 2.7.11.30; FLJ41585; FLJ76945; PPH1BMR2; T-ALK; type II activin receptor-like kinase; type II receptor for bone morphogenetic protein-4

Molecular Weight

Mass (kDA):
115.201 kDA

Genomic Context

Human
Location:	2q33.1-q33.2
Sequence:	2; NC_000002.12 (202376310..202567751)

Tissue Specificity

Highly expressed in heart and liver.

Subcellular Localizations

Cell membrane; Single-pass type I membrane protein.

Diseases

• Hypertensive Disease
• Pulmonary Hypertension
• Idiopathic Pulmonary Hypertension
• Malignant Neoplasms
• Neoplasms
• Inflammation
• Hypertrophy
• Hereditary Hemorrhagic Telangiectasia
• Hypoxia
• Vascular Diseases
• Telangiectasis

• Heart Failure
• Hiv Infections
• Pathologic Vasoconstriction
• Right Ventricular Hypertrophy
• Right Ventricular Failure
• Anoxia

Interacting Proteins

• C4bpa
• GDF5
• Prkcb
• PRKG1

Pathways

• Pathogenesis
• Cell Proliferation
• Localization
• Cell Growth
• Cell Differentiation
• Vasoconstriction
• Angiogenesis
• Muscle Cell Proliferation
• Smooth Muscle Cell Proliferation
• Translation
• Regeneration
• Cell Cycle
• Ovulation

• Osteoblast Differentiation
• Ossification
• Endochondral Ossification
• Gastrulation
• Secretion
• Neurogenesis
• Inflammatory Response

PTMs

• Phosphorylation
• Cleavage
• Ubiquitination
• Reduction

• Methylation
• Oxidation
• Myristoylation
• Iodination

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/BMPR2

Best Uses of the BMPR2 Marker in Clinical Trials

The BMPR2 gene responds to a variety stimulations, including IL-1 PMA and E2. We will be discussing the various studies on BMPR2 that were done in different cell types. We will also discuss methods used to quantify BMPR2 transcription levels. We will also discuss the best uses of BMPR2 markers in clinical trials.

BMPR2 gene expression laboratory experiments

Boster Bio researchers used a realtime RTPCR to measure BMPR2 expression. Total cellular RNA (TCRNA) was reverse-transcribed to cDNA. Invitrogen Superscript III, a cDNA-synthesis kit, was used. Each specimen was subject to a Taqman realtime PCR assay. It was developed using Primer Express software and a WT Taqman probe. For each specimen, an amplification efficiency exceeding 99.5% was achieved.

These experiments also revealed that BMPR2 expression was lower in lymphocytes, whole lungs, and female mice's BMPR2 gene. A gel-shift test showed that BMPR2 genes were less expressed when there was more estrogen. In cell culture, BMPR2 expression was decreased by higher estrogen levels. This decrease is most likely due direct binding of estrogen receptor Alpha with the BMPR2 enhancer. These results suggest that a decreased expression of BMPR2 genes in females may be associated with an increased risk for PAH.

These studies also revealed that estrogens can reduce BMPR2 mRNA in various types of normal human cell types. The study revealed that 1 mM E2 decreased BMPR2 mRNA transcription in human lymphocytes. Different amounts of E3 were also shown reduce BMPR2 mRNA expression. These findings should not be taken as a sign of cancer risk.

The BMPR2 promoter contains an estrogen response element, which is highly conserved between species. The EMSA was performed on nuclear extracts of NMuMG cells, which were chosen for their TGF-ss competence and prior validation of BMPR2 gene expression. As a positive check, vitellogenin was used. In addition to the gene test, Boster Bio BMPR2 promoter oligonucleotide induced the expression of vitellogenin.

Boster Bio's BMPR2 gene expression panel used B cells from PAH patients and their non-mutant family members. Researchers could study gene expression without the need for drugs by using these B-cells. Gene expression was also assessed via RT-PCR and quantitative RTPCR. Additional statistical analysis was also performed. There was strong evidence to support the hypothesis that BMPR2's gene expression is genetically controlled.

These results suggest that BMPR2 may be affected in some way by differential estrogen receptor expression. A similar study was conducted on female mice and found that ovariectomized women had higher levels of ERa as well as ERb than male mice. This could provide insight into the role of estrogens in PAH pathogenesis. Although these results have not been replicated in humans yet, they are promising and worth further investigation.

Study of the BMPR2 gene response to PMA/E2

In this study, we investigated the BMPR2 gene expression in human BMuMG cells using real-time RT-PCR. To accomplish this, we created cDNA using total cellular DNA using an Invitrogen Superscript III kit for cDNA Synthesis. Next, we created a Taqman PCR assay using the Primer Express package. We optimized the Taqman RTPCR for BMPR2 expression by using the WT–Taqman probe. Moreover, we checked the amplification efficiency of each specimen using the standard curve method.

Transgenic COS-7 COS-7 mice were used to test BMPR2 mRNA expression. They are devoid of estrogen receptors. We also used a BMPR2 promoter/luciferase reporter plasmid and transfected ER plasmids. Transfection of ER plasmids reduced luciferase expression and BMPR2 when normalized with tk - Renella.

A mutation in the BMPR2 gene may also cause pulmonary arterial hypertension. This is a condition that causes high blood pressure in a pulmonary artery. Some mutations prevent the receptor reaching the cell's surface while others alter its formation. In addition, pulmonary artery remodelling is often associated with pulmonary hypertension. These mutations of BMPR2 are likely a major factor in the development and progression of this disease.

Experiments where the patient's PBMCs were grown with TGF-2 and BMP2 in addition to being exposed to PMA, E2 and E2 resulted a significantly lower BMPR2 level than the age-matched controls. BMPR2 signaling has been linked to a variety of diseases and phenotypic as well as behavioral traits that are related with PAH.

M Melner generously provided a chromosomal plasmid in order to determine BMPR2 expression in BMPR2 Cells. Qiagen's RNAeasy Protect mini-kit extracted RNA. Using the BLAST technique, RNAeasy primers have been designed. This study used a cloning technique to analyze the data and determine amplification efficiency.

This study demonstrated the role played by BMPR2 in pulmonary hypertension. Familial pulmonary artery Hypertension can be caused if BMPR2 mutations occur. Further studies are needed to determine whether BMPR2 mutants are involved in this condition. It is important for you to know that the gene is closely connected with low levels AMH in young life. Low serum levels of AMH may be associated with lower basal AMHR2 expression in females. The subsequent increase in serum AMH in adolescence might enhance AMH/AMHR2-dependent Smad signaling.

This study found that BMPR2 expression was present in human lymphocytes (and pulmonary micrvascular endothelial and cell (PMVECs), respectively. This gene's mRNA level was lower than that of HPRT, which is the housekeeping gene. These results are consistent to previous findings. It was also found that FOXF1, a common gene involved with angiogenesis and DNA repair, was also downregulated.

BMPR2 gene expression studies in response to IL-1

A series BMPR2 gene expression experiments has shown that this protein plays an essential role in the development and maintenance of vascular hypertension. This protein can also be induced by IL-1. These studies also revealed that recombinant BMP9 can induce BMPR2 in blood-derived circulating ECs taken from PAH patients. These results also showed that BMPs could have beneficial hemodynamic and anti-remodeling effects in surrogate PH animals. These results show that BMPs have unique effects upon the primary endothelium. It may be necessary to take a more individual approach to assess their impact.

We first created a model for human PAECs in order to determine the effects on lentivirus-mediated disease. To do this, we used an eGFP-tagged adenoviral vector with a cytomegalovirus promoter (AdAlox5), and AdGFP or shGFP-targeted lentiviral short hairpin RNA as control vectors. We determined the fold-difference of genes greater than 50% during this time. We also assessed the levels of cleaved caspa3 and analyzed the effects lentivirus mediated proliferative phenotypes and increased cell immunity.

These studies show that PAH is a genetic disorder despite the fact that there are no mutations in BMPR2 genes. However, pulmonary inflammation induced from this disease was able s to induce IL-1-dependent LEukotrienes synthesis in Bmpr2 untreated rats. This explains how environmental injury can cause genetic mutation.

Despite the lack of functional BMPR2, AdAlox5 induced 5-LO synthesis in a variety rat cells. A transgene called GFP tagged AdAlox5 was used for monitoring the expression of this protein among Bmpr2 mutant rats. The transgene was found in epithelial cells and alveoli by week two. However, the viral load declined and was nearly absent at week three.

PAECs expressing a deficient BMPR2 gene were transformed into disease neointima in less than a week. These PAECs synthesized a protein called 5-LO that is nuclear envelope-localized and nonviral. The diseased Neointima also contained cells that expressed this protein. These cells were also prevalent in the pulmonary lesion of Bmpr2-mutant HPAH patients.

In a study on rats with Bmpr2 Haploinsufficiency, intratracheal administration of an adenovirus which expressed 5-LO caused severe levels of PAH. Additionally, severe PAH was observed in Bmpr2+/D527bp animals. Wild-type controls were unaffected. These results are encouraging and show that PAH can be caused when Bmpr2 is deficient. Moreover, despite not having BMPR2 gene, 5-LO-mediated inflammation induced pulmonary artery cell deficiency. This led to a high number neointimal and vascular cells.

Zinc Finger nuclease technology was used for the development of inbred F344 Bmpr2 mutated rats. It was found that BMPR2 expression in PAH cells was significantly higher than in controls. They also showed distinct activation patterns when compared to controls. These data indicate that BMP-dependent signaling can be controlled by differences in tissue microenvironments and spatial variations within the lung. Moreover downstream activation of SMADs did not require distinct responses in PAH-cells, indicating that alternative adaptive mechanisms could fine-tune the microvascular ECs response to BMP ligands.