type ii bone morphogenetic protein receptors

Summary

Summary: A subtype of bone morphogenetic protein receptors with low affinity for BONE MORPHOGENETIC PROTEINS. They are constitutively active PROTEIN-SERINE-THREONINE KINASES that can interact with and phosphorylate TYPE I BONE MORPHOGENETIC PROTEIN RECEPTORS.

Top Publications

  1. 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 publisher
    ..Greater endothelial injury and an enhanced inflammatory response could be the underlying causes of the sensitivity and may work in concert with BMPR2 heterozygosity to promote the development of persistent pulmonary hypertension. ..
  2. Rodriguez Murillo L, Subaran R, Stewart W, Pramanik S, Marathe S, Barst R, et al. Novel loci interacting epistatically with bone morphogenetic protein receptor 2 cause familial pulmonary arterial hypertension. J Heart Lung Transplant. 2010;29:174-80 pubmed publisher
    ..Our findings suggest that genotypes at loci in the newly identified regions, especially at 3q22, could improve FPAH risk prediction in FPAH families. We also suggest other targets for therapeutic intervention. ..
  3. Girerd B, Montani D, Coulet F, Sztrymf B, Yaici A, Jais X, et al. Clinical outcomes of pulmonary arterial hypertension in patients carrying an ACVRL1 (ALK1) mutation. Am J Respir Crit Care Med. 2010;181:851-61 pubmed publisher
    ..Despite less severe initial hemodynamics and similar management, these patients had worse prognosis compared with other patients with PAH, suggesting more rapid disease progression. ..
  4. Machado R, Eickelberg O, Elliott C, Geraci M, Hanaoka M, Loyd J, et al. Genetics and genomics of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54:S32-42 pubmed publisher
  5. Morrell N, Adnot S, Archer S, Dupuis J, Jones P, MacLean M, et al. Cellular and molecular basis of pulmonary arterial hypertension. J Am Coll Cardiol. 2009;54:S20-31 pubmed publisher
  6. Hamid R, Cogan J, Hedges L, Austin E, Phillips J, Newman J, et al. Penetrance of pulmonary arterial hypertension is modulated by the expression of normal BMPR2 allele. Hum Mutat. 2009;30:649-54 pubmed publisher
    ..Furthermore, our study illustrates a novel application of lymphoblastoid cell lines in the study of PAH, especially important because the affected site, that is, the lung, is not available for unaffected mutation carriers. ..
  7. Song Y, Jones J, Beppu H, Keaney J, Loscalzo J, Zhang Y. Increased susceptibility to pulmonary hypertension in heterozygous BMPR2-mutant mice. Circulation. 2005;112:553-62 pubmed
    ..BMPR2(+/-) mice do not develop pulmonary hypertension spontaneously; however, under inflammatory stress, they are more susceptible to an increase in RVSP, thromboxane A2 production, and vascular remodeling than wild-type mice. ..
  8. Austin E, Phillips J, Cogan J, Hamid R, Yu C, Stanton K, et al. Truncating and missense BMPR2 mutations differentially affect the severity of heritable pulmonary arterial hypertension. Respir Res. 2009;10:87 pubmed publisher
    ..These findings suggest that treatment and prevention strategies directed specifically at BMPR2 pathway defects may need to vary according to the type of mutation. ..
  9. Austin E, Cogan J, West J, Hedges L, Hamid R, Dawson E, et al. Alterations in oestrogen metabolism: implications for higher penetrance of familial pulmonary arterial hypertension in females. Eur Respir J. 2009;34:1093-9 pubmed publisher
    ..Further investigation of the role of oestrogens in this disease with profound sex bias may yield new insights and, perhaps, therapeutic interventions. ..

More Information

Publications61

  1. Talati M, West J, Blackwell T, Loyd J, Meyrick B. BMPR2 mutation alters the lung macrophage endothelin-1 cascade in a mouse model and patients with heritable pulmonary artery hypertension. Am J Physiol Lung Cell Mol Physiol. 2010;299:L363-73 pubmed publisher
    ..This is the first description of protein expression that distinguishes HPAH from IPAH in patients. ..
  2. Upton P, Morrell N. TGF-beta and BMPR-II pharmacology--implications for pulmonary vascular diseases. Curr Opin Pharmacol. 2009;9:274-80 pubmed publisher
    ..We address the possible contribution of inflammation in disease progression and focus on potential emerging therapeutic targets. ..
  3. Toshner M, Tajsic T, Morrell N. Pulmonary hypertension: advances in pathogenesis and treatment. Br Med Bull. 2010;94:21-32 pubmed publisher
    ..Areas of research may yield therapeutic benefits in the not-too-distant future, including anti-proliferative therapies and stem cell therapy. ..
  4. Portillo K, Santos S, Madrigal I, Blanco I, Pare C, Borderias L, et al. [Study of the BMPR2 gene in patients with pulmonary arterial hypertension]. Arch Bronconeumol. 2010;46:129-34 pubmed publisher
    ..The decrease in the K(CO) observed in asymptomatic carriers of the mutation suggests a certain level of pulmonary vascular changes, therefore its measurement could be useful in the familial study of FPAH. ..
  5. MacLean M, Dempsie Y. The serotonin hypothesis of pulmonary hypertension revisited. Adv Exp Med Biol. 2010;661:309-22 pubmed publisher
    ..There is also evidence to suggest that serotonin may interact with the bone morphogenetic receptor type II (BMPRII) to provide a 'second hit' risk factor for PAH. ..
  6. West J. Cross talk between Smad, MAPK, and actin in the etiology of pulmonary arterial hypertension. Adv Exp Med Biol. 2010;661:265-78 pubmed publisher
    ..We thus hypothesize that BMPR2 mutation thus leads to an impaired ability to terminate the injury repair process, leading to strong predisposition to PAH. ..
  7. Qin W, Zhao B, Shi Y, Yao C, Jin L, Jin Y. BMPRII is a direct target of miR-21. Acta Biochim Biophys Sin (Shanghai). 2009;41:618-23 pubmed
    ..These findings suggest that miR-21 may have a potential role in regulating the malignancy and metastatic abilities of prostate cancer cells and in self-renewal of stem cells by regulating the expression of BMPRII. ..
  8. Neuman N, Ma S, Schnitzler G, Zhu Y, Lagna G, Hata A. The four-and-a-half LIM domain protein 2 regulates vascular smooth muscle phenotype and vascular tone. J Biol Chem. 2009;284:13202-12 pubmed publisher
    ..Finally, aortic rings from homozygous FHL2-null mice display abnormalities in both endothelial-dependent and -independent relaxation, suggesting that FHL2 is essential for the regulation of vasomotor tone. ..
  9. Morrell N. Role of bone morphogenetic protein receptors in the development of pulmonary arterial hypertension. Adv Exp Med Biol. 2010;661:251-64 pubmed publisher
    ..This chapter summarizes the present status of our understanding of the role of BMPR-II mutations in PAH and indicates future directions for research. ..
  10. 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. ..
  11. Zhang C, Feng Y, Yang H, Koga H, Teitelbaum D. The bone morphogenetic protein signaling pathway is upregulated in a mouse model of total parenteral nutrition. J Nutr. 2009;139:1315-21 pubmed publisher
    ..The results suggest that the BMP signaling pathway may be involved in the development of intestinal mucosal atrophy due to TPN administration. ..
  12. Johnson J, Vnencak Jones C, Cogan J, Loyd J, West J. Copy-number variation in BMPR2 is not associated with the pathogenesis of pulmonary arterial hypertension. BMC Med Genet. 2009;10:58 pubmed publisher
    ..A CNV in BMPR2 was present in one African American negative control subject. We conclude that the CNV in intron 1 in BMPR2 is unlikely to play a role in the pathogenesis of either familial or sporadic PAH. NIH NCT00091546. ..
  13. Li W, Hu H. [Bone morphogenetic protein type II receptor gene promoter mutation-142G > A in a patient with familial pulmonary arterial hypertension]. Zhonghua Yi Xue Za Zhi. 2009;89:230-4 pubmed
    ..BMPR2 promoter mutation -142G > A may be associated with FPAH. ..
  14. Hong J, Lee G, Lee J, Kwon S, Park S, Kim S, et al. Effect of bone morphogenetic protein-6 on macrophages. Immunology. 2009;128:e442-50 pubmed publisher
    ..Taken together, these results demonstrate that BMP-6 regulates the proliferation and gene expression profile of macrophages. ..
  15. Hamid R, Hedges L, Austin E, Phillips J, Loyd J, Cogan J. Transcripts from a novel BMPR2 termination mutation escape nonsense mediated decay by downstream translation re-initiation: implications for treating pulmonary hypertension. Clin Genet. 2010;77:280-6 pubmed publisher
    ..Our data also suggest the need for a more thorough characterization of mutations prior to labeling them as haploinsufficient or dominant negative based simply on sequencing data. ..
  16. Tsang H, Edwards T, Wang X, Connell J, Davies R, Durrington H, et al. The hereditary spastic paraplegia proteins NIPA1, spastin and spartin are inhibitors of mammalian BMP signalling. Hum Mol Genet. 2009;18:3805-21 pubmed publisher
  17. Soon E, Holmes A, Treacy C, Doughty N, Southgate L, Machado R, et al. Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension. Circulation. 2010;122:920-7 pubmed publisher
    ..They may prove to be useful biomarkers and provide insight into the contribution of inflammation in PAH. ..
  18. Wu W, Sung J, To K, Yu L, Li H, Li Z, et al. The host defense peptide LL-37 activates the tumor-suppressing bone morphogenetic protein signaling via inhibition of proteasome in gastric cancer cells. J Cell Physiol. 2010;223:178-86 pubmed publisher
    ..This unique biological activity may open up novel therapeutic avenue for the treatment of gastric cancer. ..
  19. Herrera B, Van Dinther M, Ten Dijke P, Inman G. Autocrine bone morphogenetic protein-9 signals through activin receptor-like kinase-2/Smad1/Smad4 to promote ovarian cancer cell proliferation. Cancer Res. 2009;69:9254-62 pubmed publisher
    ..Our data indicate that BMP9 signaling through ALK2 may be a novel therapeutic target in ovarian cancer. ..
  20. Casagrande L, Demarco F, Zhang Z, Araujo F, Shi S, Nor J. Dentin-derived BMP-2 and odontoblast differentiation. J Dent Res. 2010;89:603-8 pubmed publisher
    ..Collectively, this work demonstrates that dentin-derived BMP-2 is required to induce the differentiation of SHED into odontoblasts...
  21. Sui X, Li D, Qiu H, Gaussin V, Depre C. Activation of the bone morphogenetic protein receptor by H11kinase/Hsp22 promotes cardiac cell growth and survival. Circ Res. 2009;104:887-95 pubmed publisher
    ..Therefore, potentiation of the BMP receptor by H11K promotes an activation of the PI3K/Akt pathway mediated by TAK1, which dictates the physiological effects of H11K on cardiac cell growth and survival. ..
  22. Baloira A. [Pulmonary arterial hypertension: a voyage around the year 2008]. Arch Bronconeumol. 2009;45 Suppl 1:43-8 pubmed publisher
    ..Finally, in 2008, two new consensus documents have emerged, one Spanish and the other British, which in the light of current knowledge, give a clearer insight into the management of this serious disease. ..
  23. Aramaki T, Sasai N, Yakura R, Sasai Y. Jiraiya attenuates BMP signaling by interfering with type II BMP receptors in neuroectodermal patterning. Dev Cell. 2010;19:547-61 pubmed publisher
    ..Thus, Jiraiya represents a cell-intrinsic cutoff mechanism for dynamic responsiveness to BMP signals via subtype-selective receptor control...
  24. Durrington H, Upton P, Hoer S, Boname J, Dunmore B, Yang J, et al. Identification of a lysosomal pathway regulating degradation of the bone morphogenetic protein receptor type II. J Biol Chem. 2010;285:37641-9 pubmed publisher
    ..Disruption of BMP signaling may therefore play a role in the pathobiology of diseases caused by KSHV infection, as well as KSHV-associated tumorigenesis and vascular disease. ..
  25. Alan B, Nalbantgil S. [Genetic, cellular and molecular mechanisms of pulmonary arterial hypertension]. Anadolu Kardiyol Derg. 2010;10 Suppl 1:9-13 pubmed publisher
    ..Vasoconstriction has also been shown to affect the remodeling process. Genetics, cellular and molecular basis of PAH are discussed in the paper. ..
  26. McMurtry I, Abe K, Ota H, Fagan K, Oka M. Rho kinase-mediated vasoconstriction in pulmonary hypertension. Adv Exp Med Biol. 2010;661:299-308 pubmed publisher
    ..We suspect the same will be true in at least some forms of human pulmonary arterial hypertension. ..
  27. Aldred M, Comhair S, Varella Garcia M, Asosingh K, Xu W, Noon G, et al. Somatic chromosome abnormalities in the lungs of patients with pulmonary arterial hypertension. Am J Respir Crit Care Med. 2010;182:1153-60 pubmed publisher
    ..We propose that these chromosome abnormalities may confer a growth advantage and thus contribute to the progression of PAH. ..
  28. Danesh S, Villasenor A, Chong D, Soukup C, Cleaver O. BMP and BMP receptor expression during murine organogenesis. Gene Expr Patterns. 2009;9:255-65 pubmed publisher
    ..Our studies will aid in the future design and/or interpretation of targeted deletion of individual Bmp or Bmpr genes, since this study identifies organs and tissues where redundant BMP signaling pathways are likely to occur. ..
  29. Brick K, Chen X, Lohr J, Schmidt A, Kidder L, Lew W. rhBMP-2 modulation of gene expression in infected segmental bone defects. Clin Orthop Relat Res. 2009;467:3096-103 pubmed publisher
    ..Even if infection does occur, rhBMP-2 may allow a quicker overall recovery time. ..
  30. Nicholls P, Harrison C, Gilchrist R, Farnworth P, Stanton P. Growth differentiation factor 9 is a germ cell regulator of Sertoli cell function. Endocrinology. 2009;150:2481-90 pubmed publisher
    ..Together, these results demonstrate that GDF9 and BMP15 are germ cell-specific factors in the rat testis, and that GDF9 can modulate key Sertoli cell functions. ..
  31. Hauburger A, von Einem S, Schwaerzer G, Buttstedt A, Zebisch M, Schräml M, et al. The pro-form of BMP-2 interferes with BMP-2 signalling by competing with BMP-2 for IA receptor binding. FEBS J. 2009;276:6386-98 pubmed publisher
    ..The data presented here suggest that the pro-domain of BMP-2 can alter the signalling properties of the growth factor by modulating the ability of the mature part to interact with the receptors. ..
  32. Berry A, Matthews L, Jangani M, Plumb J, Farrow S, Buchan N, et al. Interferon-inducible factor 16 is a novel modulator of glucocorticoid action. FASEB J. 2010;24:1700-13 pubmed publisher
    ..We demonstrate that IFI16 is a novel modulator of GR function and show the importance of analyzing variation in Gc sensitivity in humans, using appropriate technology, to drive discovery. ..
  33. Spiekerkoetter E, Guignabert C, de Jesus Perez V, Alastalo T, Powers J, Wang L, et al. S100A4 and bone morphogenetic protein-2 codependently induce vascular smooth muscle cell migration via phospho-extracellular signal-regulated kinase and chloride intracellular channel 4. Circ Res. 2009;105:639-47, 13 p following 647 pubmed publisher
    ..We speculate that this carefully controlled process limits signals from multiple ligands, but could be subverted in disease. ..
  34. Yamanaka R, Otsuka F, Nakamura K, Yamashita M, Otani H, Takeda M, et al. Involvement of the bone morphogenetic protein system in endothelin- and aldosterone-induced cell proliferation of pulmonary arterial smooth muscle cells isolated from human patients with pulmonary arterial hypertension. Hypertens Res. 2010;33:435-45 pubmed publisher
    ..Collectively, the functional link between BMP and ET and/or the MR system may be involved in the progress of PASMC mitosis, ultimately leading to the development of clinical PAH. ..
  35. Austin E, Loyd J, Phillips J. Genetics of pulmonary arterial hypertension. Semin Respir Crit Care Med. 2009;30:386-98 pubmed publisher
    ..This issue will become increasingly important, as clinical testing for BMPR2 mutations is now available for the evaluation of patients and family members with HPAH and IPAH. ..
  36. Toshner M, Voswinckel R, Southwood M, Al Lamki R, Howard L, Marchesan D, et al. Evidence of dysfunction of endothelial progenitors in pulmonary arterial hypertension. Am J Respir Crit Care Med. 2009;180:780-7 pubmed publisher
    ..These findings provide evidence of the involvement of progenitor cells in the vascular remodeling associated with PAH. Dysfunction of circulating progenitors in PAH may contribute to this process. ..
  37. Geraci M, Bull T, Tuder R. Genomics of pulmonary arterial hypertension: implications for therapy. Heart Fail Clin. 2010;6:101-14 pubmed publisher
    ..This article addresses the advances in the genetics of PAH, including the identification of genetic etiologies and modulators, and the role of genetics in predicting disease progression and targeting therapeutics. ..
  38. Yang J, Li X, Al Lamki R, Southwood M, Zhao J, Lever A, et al. Smad-dependent and smad-independent induction of id1 by prostacyclin analogues inhibits proliferation of pulmonary artery smooth muscle cells in vitro and in vivo. Circ Res. 2010;107:252-62 pubmed publisher
    ..Prostacyclin analogues enhance Id1 expression in vitro and in vivo and restore deficient BMP signaling in BMPR-II mutant PASMCs. ..
  39. Hall S, Brogan P, Haworth S, Klein N. Contribution of inflammation to the pathology of idiopathic pulmonary arterial hypertension in children. Thorax. 2009;64:778-83 pubmed publisher
    ..002). This study shows that pulmonary inflammation is present in the lungs of children with IPAH. This may indicate a role for inflammation in the pathobiology of IPAH and provide the rationale for novel therapeutic intervention. ..
  40. Montani D, Chaouat A. [Diagnosis and classification of pulmonary hypertension]. Presse Med. 2010;39 Suppl 1:1S3-15 pubmed publisher
    ..Schistosomiasis and chronic haemolytic anaemia have been included among the group of associated PAH. Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis have been individualized and designated as clinical group 1'. ..
  41. Wang H, Li W, Zhang W, Sun K, Song X, Gao S, et al. Novel promoter and exon mutations of the BMPR2 gene in Chinese patients with pulmonary arterial hypertension. Eur J Hum Genet. 2009;17:1063-9 pubmed publisher
  42. Yeh C, Chang C, Cheng M, Lin H, Cheng J. The antioxidative effect of bone morphogenetic protein-7 against high glucose-induced oxidative stress in mesangial cells. Biochem Biophys Res Commun. 2009;382:292-7 pubmed publisher
    ..The antioxidative activity of BMP-7 was primarily due to inhibition of PKCzeta, JNK phosphorylation, and c-jun activation. ..
  43. Yang C, Yang L, Wan M, Cao X. Generation of a mouse model with expression of bone morphogenetic protein type II receptor lacking the cytoplasmic domain in osteoblasts. Ann N Y Acad Sci. 2010;1192:286-91 pubmed publisher
    ..This study provides an in vivo tool to study the role of BMPRII in BMP/Smad signaling and the regulation of this pathway by PTH and Wnts. ..
  44. Bragdon B, Thinakaran S, Bonor J, Underhill T, Petersen N, Nohe A. FRET reveals novel protein-receptor interaction of bone morphogenetic proteins receptors and adaptor protein 2 at the cell surface. Biophys J. 2009;97:1428-35 pubmed publisher
    ..Therefore, CCPs seem to function as a negative regulatory membrane domain for BMP pathway activation. ..
  45. Rajkumar R, Konishi K, Richards T, Ishizawar D, Wiechert A, Kaminski N, et al. Genomewide RNA expression profiling in lung identifies distinct signatures in idiopathic pulmonary arterial hypertension and secondary pulmonary hypertension. Am J Physiol Heart Circ Physiol. 2010;298:H1235-48 pubmed publisher
    ..This study shows that PAH and PH secondary to IPF are characterized by distinct gene expression signatures, implying distinct pathophysiological mechanisms. ..
  46. Liu Z, Shen J, Pu K, Katus H, Plöger F, Tiefenbacher C, et al. GDF5 and BMP2 inhibit apoptosis via activation of BMPR2 and subsequent stabilization of XIAP. Biochim Biophys Acta. 2009;1793:1819-27 pubmed publisher
    ..We conclude that the inhibition of apoptosis in mouse embryonic fibroblasts by BMP2 and GDF5 does not depend on more complex signal transduction pathways such as smad and MAPK signaling but on direct stabilization of XIAP by BMPR2. ..
  47. Myllymaa S, Pasternack A, Mottershead D, Poutanen M, Pulkki M, Pelliniemi L, et al. Inhibition of oocyte growth factors in vivo modulates ovarian folliculogenesis in neonatal and immature mice. Reproduction. 2010;139:587-98 pubmed publisher
    ..We conclude that BMPR2ecd-Fc is a potent modulator of ovarian folliculogenesis in vivo, and thus, is a valuable tool for studying the physiology and downstream effects of oocyte-derived growth factors in vivo. ..
  48. Johnson M, O Connell M, Vito F, Pilcher W. Bone morphogenetic protein 4 and its receptors are expressed in the leptomeninges and meningiomas and signal via the Smad pathway. J Neuropathol Exp Neurol. 2009;68:1177-83 pubmed publisher
    ..These findings suggest that BMP-4 and BMPRs may play autocrine/paracrine roles and interact with other transforming growth factor-beta superfamily members in regulating meningioma growth and differentiation. ..
  49. 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. ..
  50. van Loon R, Roofthooft M, Van Osch Gevers M, Delhaas T, Strengers J, Blom N, et al. Clinical characterization of pediatric pulmonary hypertension: complex presentation and diagnosis. J Pediatr. 2009;155:176-82.e1 pubmed publisher
    ..Pediatric PH frequently presents with associated conditions and syndromal abnormalities. However, detailed evaluation of this complex presentation reveals that associated conditions are not always explanatory for the PH. ..
  51. Grunig E, Weissmann S, Ehlken N, Fijalkowska A, Fischer C, Fourme T, et al. Stress Doppler echocardiography in relatives of patients with idiopathic and familial pulmonary arterial hypertension: results of a multicenter European analysis of pulmonary artery pressure response to exercise and hypoxia. Circulation. 2009;119:1747-57 pubmed publisher
    ..The suitability of this trait to predict manifest PAH development should be addressed in long-term follow-up studies. ..
  52. Wang C, Roy S. Expression of bone morphogenetic protein receptor (BMPR) during perinatal ovary development and primordial follicle formation in the hamster: possible regulation by FSH. Endocrinology. 2009;150:1886-96 pubmed publisher
    ..Furthermore, FSH may regulate BMP action by modulating the expression of its receptors. ..