Genomes and Genes
Gene Symbol: Bmpr2
Description: bone morphogenetic protein receptor type 2
Alias: Bmpr-II, bone morphogenetic protein receptor type-2, bone morphogenetic protein receptor type II, bone morphogenetic protein receptor, type II (serine/threonine kinase), bone morphogenic protein receptor, type II (serine/threonine kinase)
- Upton P, Davies R, Trembath R, Morrell N. Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells. J Biol Chem. 2009;284:15794-804 pubmed publisher..This differential signaling may contribute to the contrasting pathologies of hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension. ..
- Soderstrom S, Bengtsson H, Ebendal T. Expression of serine/threonine kinase receptors including the bone morphogenetic factor type II receptor in the developing and adult rat brain. Cell Tissue Res. 1996;286:269-79 pubmed..It is suggested that the expressed receptors may mediate actions of members of the TGFbeta superfamily, e.g. BMPs, controlling the development and plasticity in the nervous system. ..
- Park S, Lee Y, Lee H, Seki T, Hong K, Park J, et al. B-cell translocation gene 2 (Btg2) regulates vertebral patterning by modulating bone morphogenetic protein/smad signaling. Mol Cell Biol. 2004;24:10256-62 pubmed..In view of the genetic evidence that reduced BMP signaling causes posteriorization of the vertebral pattern, we propose that the observed vertebral phenotype in Btg2-null mice is due to attenuated BMP signaling. ..
- Enomoto Iwamoto M, Iwamoto M, Mukudai Y, Kawakami Y, Nohno T, Higuchi Y, et al. Bone morphogenetic protein signaling is required for maintenance of differentiated phenotype, control of proliferation, and hypertrophy in chondrocytes. J Cell Biol. 1998;140:409-18 pubmed..We conclude that BMP signaling, particularly that mediated by the type II BMP receptor, is required for maintenance of the differentiated phenotype, control of cell proliferation, and expression of hypertrophic phenotype. ..
- Xie Y, Shi W, Zhou J, Gao Y, Li S, Fang Q, et al. Pulsed electromagnetic fields stimulate osteogenic differentiation and maturation of osteoblasts by upregulating the expression of BMPRII localized at the base of primary cilium. Bone. 2016;93:22-32 pubmed publisher..This study has thus revealed the molecular mechanism for the osteogenic effect of PEMFs. ..
- Charytoniuk D, Traiffort E, Pinard E, Issertial O, Seylaz J, Ruat M. Distribution of bone morphogenetic protein and bone morphogenetic protein receptor transcripts in the rodent nervous system and up-regulation of bone morphogenetic protein receptor type II in hippocampal dentate gyrus in a rat model of global cerebra. Neuroscience. 2000;100:33-43 pubmed..studies performed with specific digoxigenin-labelled riboprobes revealed the presence of bone morphogenetic protein receptor type II-positive cells throughout the brain, with a notable localization in dopaminergic cells of the ..
- Langenfeld E, Calvano S, Abou Nukta F, Lowry S, Amenta P, Langenfeld J. The mature bone morphogenetic protein-2 is aberrantly expressed in non-small cell lung carcinomas and stimulates tumor growth of A549 cells. Carcinogenesis. 2003;24:1445-54 pubmed..BMP-2 enhancement of tumor cell migration and invasion, as well as stimulating tumor growth in vivo, suggests it has important biological activity in lung carcinomas. ..
- Niessen K, Zhang G, Ridgway J, Chen H, Yan M. ALK1 signaling regulates early postnatal lymphatic vessel development. Blood. 2010;115:1654-61 pubmed publisher..Thus, our study reveals a novel aspect of ALK1 signaling in regulating lymphatic development and suggests that targeting ALK1 pathway might provide additional control of lymphangiogenesis in human diseases. ..
- Yeh C, Chang C, Cheng M, Lin H, Cheng J. Decrease of bone morphogenetic protein-7 (BMP-7) and its type II receptor (BMP-RII) in kidney of type 1-like diabetic rats. Horm Metab Res. 2009;41:605-11 pubmed publisher..Thus, we suggest that a decrease in oxidative stress is responsible for the improvement of renal function and recovery of renal BMP-7 and BMP-RII expression in streptozotocin-induced diabetic rats. ..
- Zheng Y, Ma H, Hu E, Huang Z, Cheng X, Xiong C. Inhibition of FGFR Signaling With PD173074 Ameliorates Monocrotaline-induced Pulmonary Arterial Hypertension and Rescues BMPR-II Expression. J Cardiovasc Pharmacol. 2015;66:504-14 pubmed publisher..Our data also suggest a role of FGF-2/bone morphogenetic protein signaling interaction in PAH. ..
- Southwood M, Jeffery T, Yang X, Upton P, Hall S, Atkinson C, et al. Regulation of bone morphogenetic protein signalling in human pulmonary vascular development. J Pathol. 2008;214:85-95 pubmed..Our findings support a critical role for BMPs in lung vasculogenesis. Dysfunctional BMP signalling in PAECs during development may lead to abnormal pulmonary vascular development and contribute to the pathogenesis of FPAH. ..
- Zhao J, Hedera P. Hereditary spastic paraplegia-causing mutations in atlastin-1 interfere with BMPRII trafficking. Mol Cell Neurosci. 2013;52:87-96 pubmed publisher..This, together with previously demonstrated inhibition of atlastin-1 of BMP pathway, further supports the role of this signaling cascade in axonal maintenance and axonal degeneration, which is seen in various types of HSP. ..
- Délot E, Bahamonde M, Zhao M, Lyons K. BMP signaling is required for septation of the outflow tract of the mammalian heart. Development. 2003;130:209-20 pubmed..Unlike Bmpr2-null mice, mice homozygous for this hypomorphic receptor undergo normal gastrulation, providing genetic evidence ..
- Zhou X, Wang J, Sun H, Qi Y, Xu W, Luo D, et al. MicroRNA-99a regulates early chondrogenic differentiation of rat mesenchymal stem cells by targeting the BMPR2 gene. Cell Tissue Res. 2016;366:143-53 pubmed publisher..that miR-99a targeted a putative binding site in the 3'-UTR of bone morphogenetic protein (BMP) receptor type 2 (BMPR2). Overexpression of miR-99a reduced the expression levels of BMPR2 protein...
- Beppu H, Kawabata M, Hamamoto T, Chytil A, Minowa O, Noda T, et al. BMP type II receptor is required for gastrulation and early development of mouse embryos. Dev Biol. 2000;221:249-58 pubmed..Our results suggest that the function of BMPR-II is essential for epiblast differentiation and mesoderm induction during early mouse development. ..
- Fu L, Zhou A, Huang M, Shen S, Shen J, Zhang Z, et al. A novel mutation in the BMPR2 gene in familial pulmonary arterial hypertension. Chin Med J (Engl). 2008;121:399-404 pubmed..Heterozygous mutations in the bone morphogenetic protein type II receptor gene (BMPR2) have been found to underlie a majority of FPAH cases...
- Long L, Ormiston M, Yang X, Southwood M, GrÃ¤f S, Machado R, et al. Selective enhancement of endothelial BMPR-II with BMP9 reverses pulmonary arterial hypertension. Nat Med. 2015;21:777-85 pubmed publisher..and blood outgrowth endothelial cells from subjects with PAH who bear mutations in the gene encoding BMPR-II, BMPR2. Mice bearing a heterozygous knock-in allele of a human BMPR2 mutation, R899X, which we generated as an animal ..
- Nohe A, Keating E, Underhill T, Knaus P, Petersen N. Dynamics and interaction of caveolin-1 isoforms with BMP-receptors. J Cell Sci. 2005;118:643-50 pubmed..Stimulation of starved A431 cells with BMP-2 lead to a release of caveolin-1 from the BMP receptors. We show further that the caveolin-1 beta isoform inhibits BMP signaling whereas the alpha isoform does not. ..
- Moller T, Leren T, Eiklid K, Holmstrøm H, Fredriksen P, Thaulow E. A novel BMPR2 gene mutation associated with exercise-induced pulmonary hypertension in septal defects. Scand Cardiovasc J. 2010;44:331-6 pubmed publisher..Three genes related to TGF-?, bone morphogenetic protein receptor type 2 (BMPR2), activin receptor-like kinase 1 (ALK1) and endoglin (ENG), were analyzed by DNA ..
- Schwaerzer G, Hiepen C, Schrewe H, Nickel J, Ploeger F, Sebald W, et al. New insights into the molecular mechanism of multiple synostoses syndrome (SYNS): mutation within the GDF5 knuckle epitope causes noggin-resistance. J Bone Miner Res. 2012;27:429-42 pubmed publisher..The detailed molecular characterization of GDF5-S94N as a noggin-resistant growth factor illustrates the potential of GDF5 mutants in applications with defined therapeutical needs...
- Long L, Crosby A, Yang X, Southwood M, Upton P, Kim D, et al. Altered bone morphogenetic protein and transforming growth factor-beta signaling in rat models of pulmonary hypertension: potential for activin receptor-like kinase-5 inhibition in prevention and progression of disease. Circulation. 2009;119:566-76 pubmed publisher..Inhibition of TGF-beta signaling via activin receptor-like kinase-5 prevents development and progression of PAH in the monocrotaline model and may involve inhibition of pulmonary artery smooth muscle cell migration. ..
- Edwards S, Reader K, Lun S, Western A, Lawrence S, McNatty K, et al. The cooperative effect of growth and differentiation factor-9 and bone morphogenetic protein (BMP)-15 on granulosa cell function is modulated primarily through BMP receptor II. Endocrinology. 2008;149:1026-30 pubmed..These results suggest that the initial interaction of oGDF9 and oBMP15 is with BMPRII and that a type I receptor is either recruited or already associated with BMPRII to mediate the cooperative effects of these growth factors. ..
- Ramos M, Lame M, Segall H, Wilson D. The BMP type II receptor is located in lipid rafts, including caveolae, of pulmonary endothelium in vivo and in vitro. Vascul Pharmacol. 2006;44:50-9 pubmed..Our findings indicate that BMPrII is located within lipid-dense fractions of pulmonary endothelial cell membranes with a portion present in caveolae suggesting potential dynamic regulatory structural relationships. ..
- Wang H, Ji R, Meng J, Cui Q, Zou W, Li L, et al. Functional changes in pulmonary arterial endothelial cells associated with BMPR2 mutations. PLoS ONE. 2014;9:e106703 pubmed publisher..Germline mutations in the bone morphogenetic protein receptor type 2 (BMPR2) gene are a major risk factor for developing PAH...
- Lewen A, Soderstrom S, Hillered L, Ebendal T. Expression of serine/threonine kinase receptors in traumatic brain injury. Neuroreport. 1997;8:475-9 pubmed..These data suggest that type I and type II receptors act together in signal transduction in vivo and that BMPs may be involved in neuronal plasticity after traumatic brain injury. ..
- Dewachter L, Adnot S, Guignabert C, Tu L, Marcos E, Fadel E, et al. Bone morphogenetic protein signalling in heritable versus idiopathic pulmonary hypertension. Eur Respir J. 2009;34:1100-10 pubmed publisher..Most heterogeneous BMPR-2 mutations are associated with defective Smad signalling compensated for by an activation of p38MAPK signalling, accounting for PASMC proliferation and deficient apoptosis. ..
- Tsujii M, Akeda K, Iino T, Uchida A. Are BMPs involved in normal nerve and following transection?: a pilot study. Clin Orthop Relat Res. 2009;467:3183-9 pubmed publisher..BMPRs were also upregulated compared with the normal nerve. The upregulation in BMP expression after nerve transection suggests that BMPs may play a role in the healing response of the peripheral nerve. ..
- Kariyawasam H, Xanthou G, Barkans J, Aizen M, Kay A, Robinson D. Basal expression of bone morphogenetic protein receptor is reduced in mild asthma. Am J Respir Crit Care Med. 2008;177:1074-81 pubmed publisher..Allergen provocation increases expression of the regulatory ligand BMP-7, activates BMP signaling, and increases receptor expression, all of which may contribute to repair and control of inflammation. ..
- Cheng G, Wang X, Li Y, He L. Let-7a-transfected mesenchymal stem cells ameliorate monocrotaline-induced pulmonary hypertension by suppressing pulmonary artery smooth muscle cell growth through STAT3-BMPR2 signaling. Stem Cell Res Ther. 2017;8:34 pubmed publisher..and activators of transcription 3 (STAT3) and increased its downstream bone morphogenetic protein receptor 2 (BMPR2) expression...
- Engelhard C, Sarsfield S, Merte J, Wang Q, Li P, Beppu H, et al. MEGF8 is a modifier of BMP signaling in trigeminal sensory neurons. elife. 2013;2:e01160 pubmed publisher..Thus, our data suggest that Megf8 is involved in mediating BMP4 signaling and guidance of developing TG axons. DOI:http://dx.doi.org/10.7554/eLife.01160.001. ..
- Wang Y, Zhang X, Wang H. Involvement of BMPR2 in the protective effect of fluoxetine against monocrotaline-induced endothelial apoptosis in rats. Can J Physiol Pharmacol. 2011;89:345-54 pubmed publisherMutations in bone morphogenetic protein (BMP) receptor II (BMPR2) are associated with the apoptosis of the pulmonary artery endothelial cells and the loss of the pulmonary small vessels...
- Ramos M, Lame M, Segall H, Wilson D. Smad signaling in the rat model of monocrotaline pulmonary hypertension. Toxicol Pathol. 2008;36:311-20 pubmed publisherMutations in the bone morphogenetic protein receptor type II (BMPrII) gene have been implicated in the development of familial pulmonary artery hypertension (PAH)...
- Long L, Yang X, Southwood M, Lu J, Marciniak S, Dunmore B, et al. Chloroquine prevents progression of experimental pulmonary hypertension via inhibition of autophagy and lysosomal bone morphogenetic protein type II receptor degradation. Circ Res. 2013;112:1159-70 pubmed publisher..Chloroquine and hydroxychloroquine exert beneficial effects in experimental PAH. The mechanism of action includes inhibition of autophagy pathways and inhibition of lysosomal degradation of BMPR-II. ..
- Gosemann J, Friedmacher F, Fujiwara N, Alvarez L, Corcionivoschi N, Puri P. Disruption of the bone morphogenetic protein receptor 2 pathway in nitrofen-induced congenital diaphragmatic hernia. Birth Defects Res B Dev Reprod Toxicol. 2013;98:304-9 pubmed publisher..Bone morphogenetic protein receptor 2 (BMPR2) plays a key role in pulmonary vasculogenesis during the late stages of fetal lung development...
- Lavery K, Swain P, Falb D, Alaoui Ismaili M. BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells. J Biol Chem. 2008;283:20948-58 pubmed publisher..in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. BMPR1B and ACVR2B were expressed at low levels and were not found to play a significant role in signaling by any ..
- Faber S, Robinson M, Makarenkova H, Lang R. Bmp signaling is required for development of primary lens fiber cells. Development. 2002;129:3727-37 pubmed..We conclude that Bmp signaling is required for primary lens fiber cell differentiation and, given the asymmetry of the differentiation inhibition, that distinct differentiation stimuli may be active in different quadrants of the eye. ..
- Song Y, Coleman L, Shi J, Beppu H, Sato K, Walsh K, et al. Inflammation, endothelial injury, and persistent pulmonary hypertension in heterozygous BMPR2-mutant mice. Am J Physiol Heart Circ Physiol. 2008;295:H677-90 pubmed publisherHeterozygous bone morphogenetic protein receptor-II-knockout (BMPR2(+/-)) mice have a similar genetic trait like that in some idiopathic pulmonary arterial hypertension patients...
- Lopez Lopez J, Moral Sanz J, Frazziano G, Gomez Villalobos M, Moreno L, Menendez C, et al. Type 1 diabetes-induced hyper-responsiveness to 5-hydroxytryptamine in rat pulmonary arteries via oxidative stress and induction of cyclooxygenase-2. J Pharmacol Exp Ther. 2011;338:400-7 pubmed publisher..After 6 weeks, diabetic animals showed a down-regulation of the lung bone morphogenetic protein receptor type 2, up-regulation of 5-hydroxytryptamine (5-HT) 2A receptors and cyclooxygenase-2 (COX-2) proteins ..
- Zhang Y, Wang Y, Yang K, Tian L, Fu X, Wang Y, et al. BMP4 increases the expression of TRPC and basal [Ca2+]i via the p38MAPK and ERK1/2 pathways independent of BMPRII in PASMCs. PLoS ONE. 2014;9:e112695 pubmed publisher..Thus, we concluded that BMP4 activated Smad1/5/8 pathway is BMPRII-dependent, while the BMP4 - ERK/p-P38 - TRPC - SOCE signaling axis are likely mediated through other receptor rather than BMPRII. ..
- Onishi T, Ishidou Y, Nagamine T, Yone K, Imamura T, Kato M, et al. Distinct and overlapping patterns of localization of bone morphogenetic protein (BMP) family members and a BMP type II receptor during fracture healing in rats. Bone. 1998;22:605-12 pubmed..Thus, these findings suggested that BMPs acting through their BMP receptors may play major roles in modulating the sequential events leading to bone formation. ..
- Morrell N, Yang X, Upton P, Jourdan K, Morgan N, Sheares K, et al. Altered growth responses of pulmonary artery smooth muscle cells from patients with primary pulmonary hypertension to transforming growth factor-beta(1) and bone morphogenetic proteins. Circulation. 2001;104:790-5 pubmed..We conclude that PASMCs from patients with PPH exhibit abnormal growth responses to TGF-beta(1) and BMPs and that altered integration of TGF-beta superfamily growth signals may contribute to the pathogenesis of PPH. ..
- Bosukonda D, Shih M, Sampath K, Vukicevic S. Characterization of receptors for osteogenic protein-1/bone morphogenetic protein-7 (OP-1/BMP-7) in rat kidneys. Kidney Int. 2000;58:1902-11 pubmed..OP-1 does not share receptor binding properties with other growth factors, including BMP-2 and CDMP-1, suggesting that its mode of action in kidney appears to be specific. ..
- Indjeian V, Kingman G, Jones F, Guenther C, Grimwood J, Schmutz J, et al. Evolving New Skeletal Traits by cis-Regulatory Changes in Bone Morphogenetic Proteins. Cell. 2016;164:45-56 pubmed publisher..Both gain and loss of regulatory elements can localize BMP changes to specific anatomical locations, providing a flexible regulatory basis for evolving species-specific changes in skeletal form. ..
- Yamada H, Obata H, Kaji Y, Yamashita H. Expression of transforming growth factor-beta superfamily receptors in developing rat eyes. Jpn J Ophthalmol. 1999;43:290-4 pubmed..The results suggest that the expression of TGF-beta superfamily is regulated along with retinal development and may be related to retinal development. ..