The bone morphogenetic protein receptor, type IA also known as BMPR1A is a protein which in humans is encoded by the BMPR1Agene. BMPR1A has also been designated as CD292 (cluster of differentiation 292).
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 heteromeric 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 embyonic 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 BMR1A it has been shown that it plays a role in cell differentiation. Signals tranduced 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.
^ abcdMishina Y, Starbuck MW, Gentile MA, Fukuda T, Kasparcova V, Seedor JG, Hanks MC, Amling M, Pinero GJ, Harada S, Behringer RR (2004). "Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling". J. Biol. Chem.279 (26): 27560–6. doi:10.1074/jbc.M404222200. PMID15090551.
^Nickel J, Dreyer MK, Kirsch T, Sebald W (2001). "The crystal structure of the BMP-2:BMPR-IA complex and the generation of BMP-2 antagonists". J Bone Joint Surg Am. 83-A Suppl 1 (Pt 1): S7–14. PMID11263668.
^Kirsch T, Nickel J, Sebald W; Nickel J; Sebald W (February 2000). "Isolation of recombinant BMP receptor IA ectodomain and its 2:1 complex with BMP-2". FEBS Lett.468 (2-3): 215–9. PMID10692589.
ten Dijke P, Ichijo H, Franzén P et al. (1993). "Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity". Oncogene8 (10): 2879–87. PMID8397373.
Ishidou Y, Kitajima I, Obama H et al. (1996). "Enhanced expression of type I receptors for bone morphogenetic proteins during bone formation". J. Bone Miner. Res.10 (11): 1651–9. doi:10.1002/jbmr.5650101107. PMID8592941.
Nishitoh H, Ichijo H, Kimura M et al. (1996). "Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5". J. Biol. Chem.271 (35): 21345–52. doi:10.1074/jbc.271.35.21345. PMID8702914.
Erlacher L, McCartney J, Piek E et al. (1998). "Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis". J. Bone Miner. Res.13 (3): 383–92. doi:10.1359/jbmr.19126.96.36.1993. PMID9525338.
Zhang D, Mehler MF, Song Q, Kessler JA (1998). "Development of bone morphogenetic protein receptors in the nervous system and possible roles in regulating trkC expression". J. Neurosci.18 (9): 3314–26. PMID9547239.
Ide H, Saito-Ohara F, Ohnami S et al. (1998). "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. doi:10.1159/000015048. PMID9730621.
Souchelnytskyi S, Nakayama T, Nakao A et al. (1998). "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. doi:10.1074/jbc.273.39.25364. PMID9738003.
You L, Kruse FE, Pohl J, Völcker HE (1999). "Bone morphogenetic proteins and growth and differentiation factors in the human cornea". Invest. Ophthalmol. Vis. Sci.40 (2): 296–311. PMID9950587.
Aström AK, Jin D, Imamura T et al. (1999). "Chromosomal localization of three human genes encoding bone morphogenetic protein receptors". Mamm. Genome10 (3): 299–302. doi:10.1007/s003359900990. PMID10051328.
Ebisawa T, Tada K, Kitajima I et al. (2000). "Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation". J. Cell. Sci.112 (20): 3519–27. PMID10504300.
Kim IY, Lee DH, Ahn HJ et al. (2000). "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. PMID10850425.
Wan M, Shi X, Feng X, Cao X (2001). "Transcriptional mechanisms of bone morphogenetic protein-induced osteoprotegrin gene expression". J. Biol. Chem.276 (13): 10119–25. doi:10.1074/jbc.M006918200. PMID11139569.