Biology:BMPR1A

Short description: Bone morphogenetic protein receptor

Generic protein structure example

The bone morphogenetic protein receptor, type IA also known as BMPR1A is a protein which in humans is encoded by the BMPR1A gene. BMPR1A has also been designated as CD292 (cluster of differentiation 292).

Function

The bone morphogenetic protein (BMP) receptors are a family of transmembrane serine/threonine kinases that include the type I receptors BMPR1A (this protein) and BMPR1B and the type II receptor BMPR2. These receptors are also closely related to the activin receptors, ACVR1 and ACVR2. The ligands of these receptors are members of the TGF beta superfamily. TGF-betas and activins transduce their signals through the formation of heterodimeric complexes with 2 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.

BMP's repress WNT signaling to maintain stable stem cell populations. BMPR1A null mice died at embryonic day 8.0 without mesoderm specification, demonstrating its vital role in gastrulation. It has been demonstrated in experiments using dominant negative BMPR1A chick embryos that BMPR1A plays a role in apoptosis and adipocyte development. Using constitutively active forms of BMPR1A, it has been shown that BMPR1A plays a role in cell differentiation. Signals transduced by the BMPR1A receptor are not essential for osteoblast formation or proliferation; however, BMPR1A is necessary for the extracellular matrix deposition by osteoblasts. In the chick embryo, BMPR1A receptors are found in low levels in limb bud mesenchyme, a differing location to BMPR1B, supporting the differing roles they play in osteogenesis.

Ligands

• Agonists: BMP2, BMP4, BMP6, BMP7, GDF6
• Antagonists: Noggin, Chordin

Diseases

BMPR1A, SMAD4 and PTEN are responsible for juvenile polyposis syndrome, juvenile intestinal polyposis and Cowden's disease.

Interactions

BMPR1A has been shown to interact with:

• BMP2,
• SF3B4, and
• ZMYND11.

Further reading

• "Human type II receptor for bone morphogenic proteins (BMPs): extension of the two-kinase receptor model to the BMPs". Mol. Cell. Biol. 15 (7): 3479–86. 1995. doi:10.1128/mcb.15.7.3479. PMID 7791754. 
• "Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity". Oncogene 8 (10): 2879–87. 1993. PMID 8397373. 
• "Enhanced expression of type I receptors for bone morphogenetic proteins during bone formation". J. Bone Miner. Res. 10 (11): 1651–9. 1996. doi:10.1002/jbmr.5650101107. PMID 8592941. 
• "Bone morphogenetic protein type IB receptor is progressively expressed in malignant glioma tumours". Br. J. Cancer 73 (5): 624–9. 1996. doi:10.1038/bjc.1996.108. PMID 8605097. 
• "Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5". J. Biol. Chem. 271 (35): 21345–52. 1996. doi:10.1074/jbc.271.35.21345. PMID 8702914. 
• "Analysis of the native murine bone morphogenetic protein serine threonine kinase type I receptor (ALK-3)". J. Cell. Physiol. 168 (2): 453–61. 1996. doi:10.1002/(SICI)1097-4652(199608)168:2<453::AID-JCP24>3.0.CO;2-2. PMID 8707881. 
• "Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis". J. Bone Miner. Res. 13 (3): 383–92. 1998. doi:10.1359/jbmr.1998.13.3.383. PMID 9525338. 
• "Development of bone morphogenetic protein receptors in the nervous system and possible roles in regulating trkC expression". J. Neurosci. 18 (9): 3314–26. 1998. doi:10.1523/JNEUROSCI.18-09-03314.1998. PMID 9547239. 
• "Assignment of the BMPR1A and BMPR1B genes to human chromosome 10q22.3 and 4q23→q24 byin situ hybridization and radiation hybrid map ping". Cytogenet. Cell Genet. 81 (3–4): 285–6. 1998. doi:10.1159/000015048. PMID 9730621. 
• "Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors". J. Biol. Chem. 273 (39): 25364–70. 1998. doi:10.1074/jbc.273.39.25364. PMID 9738003. 
• "Bone morphogenetic proteins and growth and differentiation factors in the human cornea". Invest. Ophthalmol. Vis. Sci. 40 (2): 296–311. 1999. PMID 9950587. 
• "Chromosomal localization of three human genes encoding bone morphogenetic protein receptors". Mamm. Genome 10 (3): 299–302. 1999. doi:10.1007/s003359900990. PMID 10051328. 
• "Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation". J. Cell Sci. 112 (20): 3519–27. 2000. doi:10.1242/jcs.112.20.3519. PMID 10504300. 
• "Expression of bone morphogenetic protein receptors type-IA, -IB and -II correlates with tumor grade in human prostate cancer tissues". Cancer Res. 60 (11): 2840–4. 2000. PMID 10850425. 
• "Crystal structure of the BMP-2-BRIA ectodomain complex". Nat. Struct. Biol. 7 (6): 492–6. 2000. doi:10.1038/75903. PMID 10881198. 
• "Transcriptional mechanisms of bone morphogenetic protein-induced osteoprotegrin gene expression". J. Biol. Chem. 276 (13): 10119–25. 2001. doi:10.1074/jbc.M006918200. PMID 11139569. 

External links

• GeneReviews/NCBI/NIH/UW entry on Juvenile Polyposis Syndrome
• BMPR1A+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
• Human BMPR1A genome location and BMPR1A gene details page in the UCSC Genome Browser.