BMP Family
Available Resources for the Study of BMP Family
Creative BioMart is committed to driving research in the field of the BMP family. Our goal is to provide researchers with the most up-to-date tools and information related to BMP modulators, BMP receptors, and BMPs.
- We offer a wide array of products including recombinant proteins, pre-coupled magnetic beads, cell and tissue lysates, and more, all of which are essential for understanding the functions and mechanisms of the BMP family.
- Our team of experts is highly experienced in BMP family research and is dedicated to creating tailored solutions to meet the specific needs of researchers.
- Additionally, we provide comprehensive resources such as involved pathways, protein function, interacting proteins, and other valuable information to support research efforts and maximize their impact.
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About BMP Family
The BMP (Bone Morphogenetic Protein) family is a group of secreted signaling molecules that belong to the larger transforming growth factor-beta (TGF-β) superfamily. BMPs play crucial roles in various biological processes, including embryonic development, tissue homeostasis, cell differentiation, and bone formation. The BMP family consists of BMP modulators, BMP receptors, and BMP ligands.
BMP Modulators
BMP modulators are extracellular proteins that regulate the availability, activity, and signaling specificity of BMP ligands.
- Some modulators, like noggin, chordin, and gremlin, bind to BMP ligands and prevent their interaction with BMP receptors, thus acting as BMP inhibitors.
- Others, such as BMP-binding proteins (BMP-BPs), enhance the signaling activity of BMPs by promoting their interaction with BMP receptors.
BMP Receptors
BMP receptors are transmembrane proteins located on the cell surface that mediate the signaling of BMP ligands. They transduce the extracellular BMP signal into intracellular signaling cascades.
There are two types of BMP receptors: type I and type II receptors.
- Type II receptors, including BMPR-II, bind BMP ligands directly and form complexes with type I receptors upon ligand binding.
- Type I receptors, such as ALK1, ALK3, ALK6, are serine/threonine kinases that become activated by phosphorylation upon ligand-induced receptor complex formation.
The activated type I receptors phosphorylate downstream signaling molecules called SMAD proteins, initiating the intracellular signaling cascade.
BMP Ligands
BMP ligands are the secreted signaling molecules that bind to BMP receptors and initiate BMP signaling.
- The BMP family consists of multiple ligands, including BMP-2, BMP-4, BMP-7, and many others.
- Each BMP ligand has its own binding specificity and can interact with specific combinations of BMP receptors.
- Upon binding to BMP receptors, ligands induce receptor complex formation, leading to intracellular signaling activation and gene expression regulation.
The interactions between BMP modulators, BMP receptors, and BMP ligands are crucial for fine-tuning BMP signaling and ensuring precise cellular responses. The balance between activators and inhibitors, as well as the specific interactions between ligands and receptors, contribute to the spatiotemporal control of BMP signaling during development and in adult tissues.
Understanding the components of the BMP family, including modulators, receptors, and ligands, provides insights into the complex mechanisms underlying BMP signaling and its implications in both normal development and disease.
Fig.1 Bone morphogenic protein (BMP) signaling in vivo. (Wang J, et al., 2022)
BMPs transduce signals through a polymeric cell surface complex of which there are two classes, type I and type II receptors. Both type I and type II receptors are single-channel transmembrane proteins with an intracellular serine/threonine kinase domain. Type II receptors phosphorylate type I receptors after ligand assembly, and the activated type I receptor recruit specific SMAD1/5/ 8 (blue pathway) and SMAD2/3 (yellow pathway), which combine with SMAD4 to form trimers which translocate to the nucleus. SMADs bind to DNA and recruit chromatin remodeling factors and tissue-specific transcription factors to regulate gene expression.
Importance of the BMP Family in Disease
Dysregulation of BMP signaling has been associated with numerous disorders, including skeletal disorders, cancer, cardiovascular diseases, and neurological conditions.
Skeletal Disorders
- BMPs are crucial for skeletal development and bone formation. Mutations or alterations in BMP signaling components can lead to skeletal abnormalities.
- Mutations in BMP receptors, such as BMPR2 mutations in hereditary pulmonary arterial hypertension (HPAH), contribute to excessive bone growth and abnormal bone morphogenesis.
- Dysregulated BMP signaling is also implicated in disorders like fibrodysplasia ossificans progressiva (FOP), a rare genetic condition characterized by the progressive formation of heterotopic bone.
Cancer
- BMPs have complex roles in cancer, acting as both tumor suppressors and tumor promoters depending on the context and tumor type.
- In some cancers, reduced expression or loss of BMP ligands and receptors is associated with tumor progression and metastasis.
- On the other hand, BMP signaling can inhibit tumor growth and metastasis by regulating cell proliferation, apoptosis, and angiogenesis.
- BMP modulators, such as noggin and gremlin, have been implicated in tumor progression by modulating BMP signaling activity.
Fig.2 Activation of BMP signaling pathways by various BMP ligands and type II and type I receptors. (Ehata S, et al., 2022)
Cardiovascular Diseases
- BMPs play critical roles in cardiovascular development and homeostasis. Dysregulated BMP signaling has been linked to cardiovascular diseases, including pulmonary arterial hypertension (PAH), atherosclerosis, and cardiac fibrosis.
- Mutations in BMP receptor genes, such as BMPR2 mutations in familial PAH, impair BMP signaling and contribute to abnormal vascular remodeling and increased pulmonary artery pressure.
- BMPs also influence cardiac tissue remodeling, valve development, and endothelial cell function, and their dysregulation can contribute to cardiovascular pathologies.
Neurological Conditions
- BMPs are involved in neural development, axon guidance, and synaptic plasticity. Alterations in BMP signaling have been implicated in neurological disorders.
- Dysregulated BMP signaling has been associated with neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, contributing to neuronal dysfunction and loss.
- BMP signaling also plays a role in spinal cord injury and neural regeneration, and modulation of this pathway holds promise for therapeutic interventions.
Understanding the role of the BMP family in disease is vital for developing targeted therapies. Modulating BMP signaling components, such as receptors, ligands, or their modulators, may offer potential therapeutic strategies for promoting tissue repair, inhibiting tumor growth, or ameliorating disease-associated abnormalities. Additionally, the BMP pathway serves as a potential diagnostic and prognostic marker in certain diseases, allowing for personalized treatment approaches.
Fig.3 BMPs induce differentiation and apoptosis of glioma-initiating cells. (Ehata S, et al., 2022)
We are committed to helping you achieve your scientific goals and make meaningful contributions to research on the roles of the various components of the BMP family and their role in disease. Contact us today to learn more about our products and resources.
References:
- Wang J, Xiao L, Wang W, et al. The Auxiliary Role of Heparin in Bone Regeneration and its Application in Bone Substitute Materials[J]. Frontiers in Bioengineering and Biotechnology, 2022, 10: 837172.
- Ehata S, Miyazono K. Bone morphogenetic protein signaling in cancer; some topics in the recent 10 years[J]. Frontiers in Cell and Developmental Biology, 2022, 10: 883523.