BMPR1A explained

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).^[1]

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.^[1]

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.^[2] It has been demonstrated in experiments using dominant negative BMPR1A chick embryos that BMPR1A plays a role in apoptosis and adipocyte development.^[2] Using constitutively active forms of BMPR1A, it has been shown that BMPR1A plays a role in cell differentiation.^[2] 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.^[2] 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.^[3]

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,^{[4] [5] [6] [7]}
• SF3B4,^[8] and
• ZMYND11.^[9]

Further reading

• Liu F, Ventura F, Doody J, Massagué J . 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 . 7791754 . 230584 . 10.1128/mcb.15.7.3479.
• ten Dijke P, Ichijo H, Franzén P, Schulz P, Saras J, Toyoshima H, Heldin CH, Miyazono K . Activin receptor-like kinases: a novel subclass of cell-surface receptors with predicted serine/threonine kinase activity . Oncogene . 8 . 10 . 2879–87 . 1993 . 8397373 .
• Ishidou Y, Kitajima I, Obama H, Maruyama I, Murata F, Imamura T, Yamada N, ten Dijke P, Miyazono K, Sakou T . Enhanced expression of type I receptors for bone morphogenetic proteins during bone formation . J. Bone Miner. Res. . 10 . 11 . 1651–9 . 1996 . 8592941 . 10.1002/jbmr.5650101107 . 33345688 .
• Yamada N, Kato M, ten Dijke P, Yamashita H, Sampath TK, Heldin CH, Miyazono K, Funa K . Bone morphogenetic protein type IB receptor is progressively expressed in malignant glioma tumours . Br. J. Cancer . 73 . 5 . 624–9 . 1996 . 8605097 . 2074358 . 10.1038/bjc.1996.108 .
• Nishitoh H, Ichijo H, Kimura M, Matsumoto T, Makishima F, Yamaguchi A, Yamashita H, Enomoto S, Miyazono K . Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5 . J. Biol. Chem. . 271 . 35 . 21345–52 . 1996 . 8702914 . 10.1074/jbc.271.35.21345 . free .
• Wu X, Robinson CE, Fong HW, Gimble JM . Analysis of the native murine bone morphogenetic protein serine threonine kinase type I receptor (ALK-3) . J. Cell. Physiol. . 168 . 2 . 453–61 . 1996 . 8707881 . 10.1002/(SICI)1097-4652(199608)168:2<453::AID-JCP24>3.0.CO;2-2 . 22669576 .
• Erlacher L, McCartney J, Piek E, ten Dijke P, Yanagishita M, Oppermann H, Luyten FP . Cartilage-derived morphogenetic proteins and osteogenic protein-1 differentially regulate osteogenesis . J. Bone Miner. Res. . 13 . 3 . 383–92 . 1998 . 9525338 . 10.1359/jbmr.1998.13.3.383 . 25307046 . free .
• Zhang D, Mehler MF, Song Q, Kessler JA . Development of bone morphogenetic protein receptors in the nervous system and possible roles in regulating trkC expression . J. Neurosci. . 18 . 9 . 3314–26 . 1998 . 9547239 . 10.1523/JNEUROSCI.18-09-03314.1998. 6792660 . free .
• Ide H, Saito-Ohara F, Ohnami S, Osada Y, Ikeuchi T, Yoshida T, Terada M . 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 . 9730621 . 10.1159/000015048 . 46751090 .
• Souchelnytskyi S, Nakayama T, Nakao A, Morén A, Heldin CH, Christian JL, ten Dijke P . 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 . 9738003 . 10.1074/jbc.273.39.25364 . free .
• You L, Kruse FE, Pohl J, Völcker HE . Bone morphogenetic proteins and growth and differentiation factors in the human cornea . Invest. Ophthalmol. Vis. Sci. . 40 . 2 . 296–311 . 1999 . 9950587 .
• Aström AK, Jin D, Imamura T, Röijer E, Rosenzweig B, Miyazono K, ten Dijke P, Stenman G . Chromosomal localization of three human genes encoding bone morphogenetic protein receptors . Mamm. Genome . 10 . 3 . 299–302 . 1999 . 10051328 . 10.1007/s003359900990 . 19132542 .
• Ebisawa T, Tada K, Kitajima I, Tojo K, Sampath TK, Kawabata M, Miyazono K, Imamura T . Characterization of bone morphogenetic protein-6 signaling pathways in osteoblast differentiation . J. Cell Sci. . 112 . 20 . 3519–27 . 2000 . 10.1242/jcs.112.20.3519 . 10504300 .
• Kim IY, Lee DH, Ahn HJ, Tokunaga H, Song W, Devereaux LM, Jin D, Sampath TK, Morton RA . 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 . 10850425 .
• Kirsch T, Sebald W, Dreyer MK . Crystal structure of the BMP-2-BRIA ectodomain complex . Nat. Struct. Biol. . 7 . 6 . 492–6 . 2000 . 10881198 . 10.1038/75903 . 19403233 .
• Wan M, Shi X, Feng X, Cao X . Transcriptional mechanisms of bone morphogenetic protein-induced osteoprotegrin gene expression . J. Biol. Chem. . 276 . 13 . 10119–25 . 2001 . 11139569 . 10.1074/jbc.M006918200 . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Juvenile Polyposis Syndrome

Notes and References

1. Web site: Entrez Gene: BMPR1A bone morphogenetic protein receptor, type IA.
2. Yuji Mishina . Mishina Y, Starbuck MW, Gentile MA, Fukuda T, Kasparcova V, Seedor JG, Hanks MC, Amling M, Pinero GJ, Harada S, Behringer RR . Bone morphogenetic protein type IA receptor signaling regulates postnatal osteoblast function and bone remodeling . J. Biol. Chem. . 279 . 26 . 27560–6 . 2004 . 15090551 . 10.1074/jbc.M404222200 . free .
3. Yoon BS, Ovchinnikov DA, Yoshii I, Mishina Y, Behringer RR, Lyons KM . Bmpr1a and Bmpr1b have overlapping functions and are essential for chondrogenesis in vivo . Proc. Natl. Acad. Sci. U.S.A. . 102 . 14 . 5062–7 . 2005 . 15781876 . 555995 . 10.1073/pnas.0500031102 . 2005PNAS..102.5062Y . free .
4. Nickel J, Dreyer MK, Kirsch T, Sebald W . 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 . 2001 . 11263668 .
5. Kirsch T, Nickel J, Sebald W . Isolation of recombinant BMP receptor IA ectodomain and its 2:1 complex with BMP-2 . FEBS Lett. . 468 . 2–3 . 215–9 . February 2000 . 10692589 . 10.1016/s0014-5793(00)01214-x . 30068719 .
6. Kirsch T, Nickel J, Sebald W . BMP-2 antagonists emerge from alterations in the low-affinity binding epitope for receptor BMPR-II . EMBO J. . 19 . 13 . 3314–24 . July 2000 . 10880444 . 313944 . 10.1093/emboj/19.13.3314 .
7. Gilboa L, Nohe A, Geissendörfer T, Sebald W, Henis YI, Knaus P . Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine kinase receptors . Mol. Biol. Cell . 11 . 3 . 1023–35 . March 2000 . 10712517 . 14828 . 10.1091/mbc.11.3.1023 .
8. Nishanian TG, Waldman T . Interaction of the BMPR-IA tumor suppressor with a developmentally relevant splicing factor . Biochem. Biophys. Res. Commun. . 323 . 1 . 91–7 . October 2004 . 15351706 . 10.1016/j.bbrc.2004.08.060 .
9. Kurozumi K, Nishita M, Yamaguchi K, Fujita T, Ueno N, Shibuya H . BRAM1, a BMP receptor-associated molecule involved in BMP signalling . Genes Cells . 3 . 4 . 257–64 . April 1998 . 9663660 . 10.1046/j.1365-2443.1998.00186.x . 29818690 .