BMPR1B Human
Description
Product Specs
Bone Morphogenetic Protein Receptor, Type IB, BMP Type-1B Receptor, EC 2.7.11.30, BMPR-1B, ALK6, Bone Morphogenetic Protein Receptor Type-1B, Serine/Threonine Receptor Kinase, CDw293 Antigen, EC 2.7.11, CDw293, ALK-6, Bone morphogenetic protein receptor type-1B.
Q&A
What is the biological function of BMPR1B in humans?
BMPR1B is a transmembrane serine/threonine kinase receptor that belongs to the BMP receptor family. It mediates signaling pathways initiated by bone morphogenetic proteins (BMPs), which are members of the TGF-beta superfamily. These pathways regulate key cellular processes such as proliferation, differentiation, apoptosis, and tissue development. BMPR1B is particularly significant in endochondral bone formation, embryogenesis, and reproductive tissue regulation . Furthermore, BMPR1B interacts with type II BMP receptors to form heteromeric complexes essential for ligand binding and signal transduction . Mutations in BMPR1B have been linked to diseases such as primary pulmonary hypertension and brachydactyly .
How does BMPR1B contribute to BMP signaling pathways?
BMPR1B functions as a type I receptor within the BMP signaling cascade. When BMP ligands bind to type II receptors, these receptors phosphorylate and activate BMPR1B. Subsequently, BMPR1B phosphorylates receptor-regulated SMAD proteins (R-SMADs), including SMAD1, SMAD5, and SMAD8. These activated R-SMADs form complexes with SMAD4 and translocate to the nucleus to regulate gene transcription . Additionally, BMPR1B can initiate non-SMAD signaling pathways such as MAPK cascades, which contribute to cellular responses beyond transcriptional regulation .
What experimental models are used to study BMPR1B?
Several experimental models have been employed to investigate BMPR1B's function:
In vitro studies
Recombinant human BMPR1B proteins are used in kinase assays to analyze its enzymatic activity and interaction with substrates like casein . These studies often utilize purified proteins expressed in systems such as Sf9 insect cells or E. coli .
Animal models
Knockdown experiments using morpholino oligonucleotides in zebrafish have demonstrated phenotypes such as ocular coloboma and microphthalmia, confirming BMPR1B's role in eye development . Mouse models are also used for genetic studies related to skeletal abnormalities and pulmonary hypertension.
Cross-species meta-analysis
Comparative studies between zebrafish and mouse datasets have identified conserved genes involved in optic fissure morphogenesis, highlighting BMPR1B's evolutionary significance .
What are the implications of BMPR1B mutations in human diseases?
Mutations in BMPR1B have been implicated in several conditions:
Skeletal disorders
BMPR1B mutations are associated with brachydactyly types A1 and A2, characterized by shortened digits due to abnormal bone development . Acromesomelic dysplasia is another condition linked to these mutations .
Pulmonary diseases
Primary pulmonary hypertension has been connected to aberrant BMP signaling mediated by defective BMPR1B receptors .
Ocular abnormalities
Recent studies have identified BMPR1B as a novel causative gene for ocular coloboma through cross-species meta-analysis. Pathogenic variants disrupt optic fissure closure during early eye development .
How can researchers analyze pathogenic variants of BMPR1B?
To study pathogenic variants of BMPR1B:
Genomic analysis
Whole-exome sequencing can identify mutations within the BMPR1B gene that correlate with specific phenotypes. For example, pathogenic variants like c.1456C>T (R486W) have been linked to brachydactyly type A2 .
Functional assays
In vitro experiments using recombinant BMPR1B proteins carrying patient-specific mutations can reveal their impact on kinase activity and substrate binding . Rescue experiments in zebrafish further validate the functional consequences of these mutations .
Database interrogation
Large-scale genomic databases such as the UK 100,000 Genomes Project provide valuable resources for identifying novel variants associated with undiagnosed conditions .
What methodologies are used for producing recombinant human BMPR1B?
Efficient production of recombinant human BMPR1B involves several steps:
Expression systems
BMPR1B is commonly expressed in systems like Sf9 insect cells or E. coli due to their ability to produce high yields of protein with specific modifications .
Purification techniques
Affinity chromatography using GST tags ensures the isolation of high-purity recombinant proteins. Additional steps like size exclusion chromatography may be employed for further refinement .
Activity assays
Kinase activity is assessed using radiometric or ADP-Glo assays under optimized conditions (e.g., specific buffer compositions and substrate concentrations) .
How does BMPR1B influence reproductive performance?
BMPR1B plays a critical role in regulating reproductive tissue development and function. Its expression has been observed in ovarian and endometrial tissues, where it contributes to follicular development and ovulation through BMP-mediated signaling pathways . Dysregulation of BMPR1B has been associated with infertility issues in both male and female subjects.
What challenges exist in studying non-canonical signaling pathways mediated by BMPR1B?
Non-canonical pathways initiated by BMPR1B include MAPK cascades that regulate cellular processes independent of SMAD transcription factors . Studying these pathways poses challenges due to their complexity:
Signal specificity
Non-SMAD signaling often overlaps with other pathways like Wnt or Notch signaling, making it difficult to isolate BMPR1B-specific effects.
Experimental limitations
Standard assays may not capture transient or context-dependent signaling events mediated by non-canonical pathways.
Therapeutic implications
Targeting non-SMAD pathways requires precise modulation without disrupting canonical BMP signaling.
How can researchers address data contradictions in studies involving BMPR1B?
Data contradictions often arise due to differences in experimental design or biological contexts:
Comparative analysis
Cross-species studies can help resolve discrepancies by identifying conserved functions of BMPR1B across different organisms .
Standardization
Using consistent methodologies for protein production, purification, and activity assays reduces variability between studies .
Meta-analysis
Aggregating data from multiple studies allows researchers to identify overarching trends despite individual inconsistencies.
What future directions exist for research on BMPR1B?
Future research on BMPR1B could focus on:
Therapeutic applications
Developing drugs that modulate BMPR1B activity may offer targeted treatments for skeletal disorders, pulmonary hypertension, and ocular abnormalities.
Regenerative medicine
Harnessing recombinant human BMPR1B for tissue engineering applications could revolutionize approaches to bone repair and organ regeneration.
Advanced modeling
Integrating single-cell transcriptomics with CRISPR-based gene editing will enable more precise investigations into BMPR1B's role across various tissues.
Product Science Overview
Bone Morphogenetic Protein Receptor-1B (BMPR1B) is a member of the bone morphogenetic protein (BMP) receptor family, which belongs to the larger transforming growth factor-beta (TGF-β) superfamily. These receptors are transmembrane serine/threonine kinases that play crucial roles in various biological processes, including embryogenesis, tissue homeostasis, and disease progression .
BMPR1B is a type I receptor that forms heteromeric complexes with type II receptors to transduce BMP signals. The receptor complex typically consists of two type I and two type II receptors. Type II receptors bind BMP ligands in the absence of type I receptors, but signaling requires the presence of both receptor types . Upon ligand binding, BMPR1B undergoes phosphorylation, which activates downstream signaling pathways, including the SMAD pathway, leading to the regulation of gene expression .
BMPR1B is involved in several critical biological processes:
- Endochondral Bone Formation: BMPR1B plays a pivotal role in the formation of bones through endochondral ossification, a process where cartilage is replaced by bone .
- Embryogenesis: During embryonic development, BMPR1B is essential for the proper formation of various tissues and organs .
- Tissue Homeostasis: BMPR1B helps maintain the balance and function of tissues in the adult organism .
Mutations in the BMPR1B gene have been associated with several diseases:
- Primary Pulmonary Hypertension: Mutations in BMPR1B can lead to primary pulmonary hypertension, a condition characterized by high blood pressure in the lungs .
- Acromesomelic Dysplasia: This genetic disorder, which affects bone growth, has also been linked to mutations in BMPR1B .
- Brachydactyly Type A1: A condition characterized by shortened fingers and toes, caused by mutations in BMPR1B .
Human recombinant BMPR1B is produced using recombinant DNA technology, which involves inserting the BMPR1B gene into a suitable expression system, such as bacteria or mammalian cells, to produce the protein in large quantities. This recombinant protein is used in various research and therapeutic applications to study BMP signaling pathways and to develop treatments for diseases associated with BMPR1B dysfunction .
