type i bone morphogenetic protein receptors


Summary: A subtype of bone morphogenetic protein receptors with high affinity for BONE MORPHOGENETIC PROTEINS. They can interact with and undergo PHOSPHORYLATION by BONE MORPHOGENETIC PROTEIN RECEPTORS, TYPE II. They signal primarily through RECEPTOR-REGULATED SMAD PROTEINS.

Top Publications

  1. Kamiya N, Ye L, Kobayashi T, Mochida Y, Yamauchi M, Kronenberg H, et al. BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway. Development. 2008;135:3801-11 pubmed publisher
  2. Twombly V, Bangi E, Le V, Malnic B, Singer M, Wharton K. Functional analysis of saxophone, the Drosophila gene encoding the BMP type I receptor ortholog of human ALK1/ACVRL1 and ACVR1/ALK2. Genetics. 2009;183:563-79, 1SI-8SI pubmed publisher
  3. Bottcher Y, Unbehauen H, Kloting N, Ruschke K, Körner A, Schleinitz D, et al. Adipose tissue expression and genetic variants of the bone morphogenetic protein receptor 1A gene (BMPR1A) are associated with human obesity. Diabetes. 2009;58:2119-28 pubmed publisher
    ..Our data suggest that genetic variation in the BMPR1A may play a role in the pathophysiology of human obesity, possibly mediated through effects on mRNA expression. ..
  4. Volkenstein S, Brors D, Hansen S, Minovi A, Laub M, Jennissen H, et al. Influence of bone morphogenetic protein-2 on spiral ganglion neurite growth in vitro. Eur Arch Otorhinolaryngol. 2009;266:1381-9 pubmed publisher
    ..In contrast, rhBMP-2 can be attached to metal surfaces without loss of activity. Our findings suggest in vivo studies and a future clinical application of rhBMP-2 in cochlear implant technology to improve the tissue/electrode interface. ..
  5. Van Dinther M, Visser N, de Gorter D, Doorn J, Goumans M, de Boer J, et al. ALK2 R206H mutation linked to fibrodysplasia ossificans progressiva confers constitutive activity to the BMP type I receptor and sensitizes mesenchymal cells to BMP-induced osteoblast differentiation and bone formation. J Bone Miner Res. 2010;25:1208-15 pubmed publisher
    ..We have generated an animal model that can be used as a stepping stone for preclinical studies aimed at inhibiting the heterotopic ossification characteristic of FOP...
  6. Self M, Geng X, Oliver G. Six2 activity is required for the formation of the mammalian pyloric sphincter. Dev Biol. 2009;334:409-17 pubmed publisher
    ..5, Sox9, and Gremlin) also appear to be required for the formation of this structure in mammals. Thus, we propose that Six2 activity regulates this gene network during the genesis of the pyloric sphincter in the mouse...
  7. Kotzsch A, Nickel J, Sebald W, Mueller T. Purification, crystallization and preliminary data analysis of ligand-receptor complexes of growth and differentiation factor 5 (GDF5) and BMP receptor IB (BRIB). Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009;65:779-83 pubmed publisher
    ..46, c = 82.78 A. Small changes in the crystallization condition resulted in crystals with a different morphology. These crystals consisted of the full ternary complex GDF5-BRIB-ActRIIB, but only diffracted to low resolution. ..
  8. Blouet C, Jo Y, Li X, Schwartz G. Mediobasal hypothalamic leucine sensing regulates food intake through activation of a hypothalamus-brainstem circuit. J Neurosci. 2009;29:8302-11 pubmed publisher
    ..Our data identify a novel, specific hypothalamus-brainstem circuit that links amino acid availability and nutrient sensing to the control of food intake. ..
  9. Ishibashi O, Ikegame M, Takizawa F, Yoshizawa T, Moksed M, Iizawa F, et al. Endoglin is involved in BMP-2-induced osteogenic differentiation of periodontal ligament cells through a pathway independent of Smad-1/5/8 phosphorylation. J Cell Physiol. 2010;222:465-73 pubmed publisher
    ..These results, taken together, raise a possibility that PDL cells respond to BMP-2 via a unique signaling pathway dependent on endoglin, which is involved in the osteoblastic differentiation and mineralization of the cells. ..

More Information


  1. Panetta N, Gupta D, Lee J, Wan D, Commons G, Longaker M. Human adipose-derived stromal cells respond to and elaborate bone morphogenetic protein-2 during in vitro osteogenic differentiation. Plast Reconstr Surg. 2010;125:483-93 pubmed publisher
    ..Future studies will examine the effect of rhBMP2 on osteogenic differentiation of human adipose-derived stromal cells in vivo. ..
  2. Zhang F, Qiu T, Wu X, Wan C, Shi W, Wang Y, et al. Sustained BMP signaling in osteoblasts stimulates bone formation by promoting angiogenesis and osteoblast differentiation. J Bone Miner Res. 2009;24:1224-33 pubmed publisher
    ..In conclusion, osteoblast targeted expression of a mutant endofin protein lacking the pp1c binding activity results in sustained signaling of the BMP type I receptor, which increases bone formation and skeletal angiogenesis. ..
  3. Hua G, Yang L. A review of research progress of FecB gene in Chinese breeds of sheep. Anim Reprod Sci. 2009;116:1-9 pubmed publisher
    ..Moreover, introducing FecB gene to some low prolific breeds of sheep by crossbreeding system can improve the reproductive traits. ..
  4. Tomayko M, Anderson S, Brayton C, Sadanand S, Steinel N, Behrens T, et al. Systematic comparison of gene expression between murine memory and naive B cells demonstrates that memory B cells have unique signaling capabilities. J Immunol. 2008;181:27-38 pubmed
    ..Thus, memory and naive B cells are intrinsically wired to signal differently from one another and express a functional signaling pathway that is known to maintain stem cells in other lineages. ..
  5. Kotzsch A, Nickel J, Seher A, Sebald W, Müller T. Crystal structure analysis reveals a spring-loaded latch as molecular mechanism for GDF-5-type I receptor specificity. EMBO J. 2009;28:937-47 pubmed publisher
    ..The new structural data now provide also a molecular basis of how phenotypically relevant missense mutations in GDF-5 might impair receptor binding and activation. ..
  6. Sahni V, Mukhopadhyay A, Tysseling V, Hebert A, Birch D, McGuire T, et al. BMPR1a and BMPR1b signaling exert opposing effects on gliosis after spinal cord injury. J Neurosci. 2010;30:1839-55 pubmed publisher
    ..Targeting specific BMPR subunits for therapeutic purposes may thus provide an approach for manipulating gliosis and enhancing functional outcomes after SCI. ..
  7. Mira H, Andreu Z, Suh H, Lie D, Jessberger S, Consiglio A, et al. Signaling through BMPR-IA regulates quiescence and long-term activity of neural stem cells in the adult hippocampus. Cell Stem Cell. 2010;7:78-89 pubmed publisher
    ..BMPs are therefore required to balance NSC quiescence/proliferation and to prevent loss of the stem cell activity that supports continuous neurogenesis in the mature hippocampus. ..
  8. 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. ..
  9. Alam N, St Arnaud R, Lauzier D, Rosen V, Hamdy R. Are endogenous BMPs necessary for bone healing during distraction osteogenesis?. Clin Orthop Relat Res. 2009;467:3190-8 pubmed publisher
    ..These data suggest endogenous BMPs are important for bone healing and manipulating endogenous BMPs may help accelerate bone consolidation during DO. ..
  10. Perotti C, Wiedl T, Florin L, Reuter H, Moffat S, Silbermann M, et al. Characterization of mammary epithelial cell line HC11 using the NIA 15k gene array reveals potential regulators of the undifferentiated and differentiated phenotypes. Differentiation. 2009;78:269-82 pubmed publisher
    ..We have identified a number of genes, of known and unknown function, that are candidates for the maintenance of the undifferentiated phenotype and for early regulators of mammary alveolar cell differentiation. ..
  11. Saetrom P, Biesinger J, Li S, Smith D, Thomas L, Majzoub K, et al. A risk variant in an miR-125b binding site in BMPR1B is associated with breast cancer pathogenesis. Cancer Res. 2009;69:7459-65 pubmed publisher
    ..Our approach is general and can help identify and explain the mechanisms behind disease association for alleles that affect miRNA regulation. ..
  12. Stottmann R, Choi M, Mishina Y, Meyers E, Klingensmith J. BMP receptor IA is required in mammalian neural crest cells for development of the cardiac outflow tract and ventricular myocardium. Development. 2004;131:2205-18 pubmed
    ..These results demonstrate that BMP2/4 signaling in mammalian neural crest derivatives is essential for outflow tract development and may regulate a crucial proliferation signal for the ventricular myocardium. ..
  13. 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. ..
  14. Wong W, Tian X, Chen Y, Leung F, Liu L, Lee H, et al. Bone morphogenic protein-4 impairs endothelial function through oxidative stress-dependent cyclooxygenase-2 upregulation: implications on hypertension. Circ Res. 2010;107:984-91 pubmed publisher
    ..This BMP4/ROS/COX-2 cascade is important in the maintenance of endothelial dysfunction in hypertension. ..
  15. Song G, Kim H, Woo K, Baek J, Kim G, Choi J, et al. Molecular consequences of the ACVR1(R206H) mutation of fibrodysplasia ossificans progressiva. J Biol Chem. 2010;285:22542-53 pubmed publisher
  16. Nomura Kitabayashi A, Phoon C, Kishigami S, Rosenthal J, Yamauchi Y, Abe K, et al. Outflow tract cushions perform a critical valve-like function in the early embryonic heart requiring BMPRIA-mediated signaling in cardiac neural crest. Am J Physiol Heart Circ Physiol. 2009;297:H1617-28 pubmed publisher
    ..This study provides definitive evidence that the outflow cushions perform a valve-like function critical for survival of the early mouse embryo. ..
  17. Cheah P, Wong Y, Chau Y, Loi C, Lim K, Lim J, et al. Germline bone morphogenesis protein receptor 1A mutation causes colorectal tumorigenesis in hereditary mixed polyposis syndrome. Am J Gastroenterol. 2009;104:3027-33 pubmed publisher
  18. Dudley B, Palumbo C, Nalepka J, Molyneaux K. BMP signaling controls formation of a primordial germ cell niche within the early genital ridges. Dev Biol. 2010;343:84-93 pubmed publisher
    ..Loss of BMP signaling leads to the loss of the PGC target resulting in reduced PGC numbers and disrupted PGC migration. ..
  19. Bragdon B, Thinakaran S, Moseychuk O, King D, Young K, Litchfield D, et al. Casein kinase 2 beta-subunit is a regulator of bone morphogenetic protein 2 signaling. Biophys J. 2010;99:897-904 pubmed publisher
    ..Signaling was initiated once CK2 was released from BRIa, leading to the mineralization of C2C12 cells. These data suggest that CK2 is a negative regulator of BMP signaling and osteoblast differentiation. ..
  20. 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. ..
  21. 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. ..
  22. Askmyr M, Sims N, Martin T, Purton L. What is the true nature of the osteoblastic hematopoietic stem cell niche?. Trends Endocrinol Metab. 2009;20:303-9 pubmed publisher
  23. Liu Y, Ren W, Warburton R, Toksoz D, Fanburg B. Serotonin induces Rho/ROCK-dependent activation of Smads 1/5/8 in pulmonary artery smooth muscle cells. FASEB J. 2009;23:2299-306 pubmed publisher
    ..Rho and Rho kinase also participate in the activation of Smads by BMP. ..
  24. Lammens J, Liu Z, Luyten F. Bone morphogenetic protein signaling in the murine distraction osteogenesis model. Acta Orthop Belg. 2009;75:94-102 pubmed
    ..The data indicate a BMP molecular profile reminiscent of the embryonic maturation process in endochondral bone formation. ..
  25. Brinkmeier M, Davis S, Carninci P, MacDonald J, Kawai J, Ghosh D, et al. Discovery of transcriptional regulators and signaling pathways in the developing pituitary gland by bioinformatic and genomic approaches. Genomics. 2009;93:449-60 pubmed publisher
    ..These genes are exciting candidates for regulators of pituitary development and function. ..
  26. Huang J, Dattilo L, Rajagopal R, Liu Y, Kaartinen V, Mishina Y, et al. FGF-regulated BMP signaling is required for eyelid closure and to specify conjunctival epithelial cell fate. Development. 2009;136:1741-50 pubmed publisher
    ..A second row of eyelashes is a feature of human lymphedema-distichiasis syndrome, which is associated with mutations in FOXC2...
  27. Edson M, Nalam R, Clementi C, Franco H, DeMayo F, Lyons K, et al. Granulosa cell-expressed BMPR1A and BMPR1B have unique functions in regulating fertility but act redundantly to suppress ovarian tumor development. Mol Endocrinol. 2010;24:1251-66 pubmed publisher
    ..These studies support a role for a functional BMP signaling axis as a tumor suppressor pathway in the ovary, with BMPR1A and BMPR1B acting downstream of BMP ligands and upstream of BMP receptor SMADs. ..
  28. Stankovic K, Adachi O, Tsuji K, Kristiansen A, Adams J, Rosen V, et al. Differences in gene expression between the otic capsule and other bones. Hear Res. 2010;265:83-9 pubmed publisher
    ..Expression levels were high for opg and bmpr1b, and minimal for bmp3 within the otic capsule. We concluded that opg and bmpr1b likely play important roles in inhibition of remodeling within the otic capsule. ..
  29. Ahmed S, Metpally R, Sangadala S, Reddy B. Virtual screening and selection of drug-like compounds to block noggin interaction with bone morphogenetic proteins. J Mol Graph Model. 2010;28:670-82 pubmed publisher
    ..By in silico screening we selected and ranked several compounds that have high theoretical scores to bind to noggin to block BMP-noggin interaction. ..
  30. Beckham J, Tuttle K, Tyler K. Reovirus activates transforming growth factor beta and bone morphogenetic protein signaling pathways in the central nervous system that contribute to neuronal survival following infection. J Virol. 2009;83:5035-45 pubmed publisher
  31. Soares A, Xavier R, da Costa Miguel M, de Souza L, Pinto L. Bone morphogenetic protein-2/4 and bone morphogenetic protein receptor type IA expression in metastatic and nonmetastatic oral squamous cell carcinoma. Am J Otolaryngol. 2010;31:266-71 pubmed publisher
  32. Ma Y, Ma L, Guo Q, Zhang S. Expression of bone morphogenetic protein-2 and its receptors in epithelial ovarian cancer and their influence on the prognosis of ovarian cancer patients. J Exp Clin Cancer Res. 2010;29:85 pubmed publisher
    ..BMP-2, BMPRIB, and BMPRII exhibited low expression in EOC tissue, and variation or loss of expression may indicate poor prognosis for ovarian cancer patients. ..
  33. Kaplan F, Pignolo R, Shore E. The FOP metamorphogene encodes a novel type I receptor that dysregulates BMP signaling. Cytokine Growth Factor Rev. 2009;20:399-407 pubmed publisher
  34. Ho C, Bernard D. Bone morphogenetic protein 2 signals via BMPR1A to regulate murine follicle-stimulating hormone beta subunit transcription. Biol Reprod. 2009;81:133-41 pubmed publisher
    ..The specific mechanism(s) through which the Booroola FecB mutation alters BMPR1B function remains to be determined. ..
  35. Little S, Mullins M. Bone morphogenetic protein heterodimers assemble heteromeric type I receptor complexes to pattern the dorsoventral axis. Nat Cell Biol. 2009;11:637-43 pubmed publisher
  36. Fukuda T, Kohda M, Kanomata K, Nojima J, Nakamura A, Kamizono J, et al. Constitutively activated ALK2 and increased SMAD1/5 cooperatively induce bone morphogenetic protein signaling in fibrodysplasia ossificans progressiva. J Biol Chem. 2009;284:7149-56 pubmed publisher
    ..Gene transfer of Smad7 or inhibition of type I receptors with dorsomorphin may represent strategies for blocking the activity induced by ALK2(R206H) in FOP...
  37. Bokobza S, Ye L, Kynaston H, Mansel R, Jiang W. Reduced expression of BMPR-IB correlates with poor prognosis and increased proliferation of breast cancer cells. Cancer Genomics Proteomics. 2009;6:101-8 pubmed
    ..This suggests that BMPR-IB mediates an inhibitory effect on breast cancer cells. ..
  38. Bobak N, Agoston Z, Schulte D. Evidence against involvement of Bmp receptor 1b signaling in fate specification of the chick mesencephalic alar plate at HH16. Neurosci Lett. 2009;461:223-8 pubmed publisher
  39. Huang H, Song T, Li X, Hu L, He Q, Liu M, et al. BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc Natl Acad Sci U S A. 2009;106:12670-5 pubmed publisher
    ..Expression of LOX is induced by BMP2/4 during adipocyte lineage commitment, and knockdown of its expression disrupts the commitment process. ..
  40. Mukhopadhyay A, McGuire T, Peng C, Kessler J. Differential effects of BMP signaling on parvalbumin and somatostatin interneuron differentiation. Development. 2009;136:2633-42 pubmed publisher
    ..Thus, BMP4 signaling through type I receptors regulates the differentiation of two major medial ganglionic eminence-derived interneuron populations and defines their relative numbers in the cortex. ..
  41. Katagiri T. [Genetic basis for skeletal disease. Establishment of novel treatments for fibrodysplasia ossificans progressiva (FOP)]. Clin Calcium. 2010;20:1204-11 pubmed publisher
    ..In patients with FOP, heterozygous mutations have been identified in the BMP type I receptor, ALK2. This finding stimulates establishment of some animal models of FOP and development of novel treatments for FOP. ..
  42. 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. ..
  43. Higashi Kovtun M, Mosca T, Dickman D, Meinertzhagen I, Schwarz T. Importin-beta11 regulates synaptic phosphorylated mothers against decapentaplegic, and thereby influences synaptic development and function at the Drosophila neuromuscular junction. J Neurosci. 2010;30:5253-68 pubmed publisher
    ..Thus, importin-beta11 function interacts with the BMP pathway to regulate a pool of pMAD that must be present at the presynapse for its proper development and function. ..
  44. Rodriguez P, da Silva S, Oxburgh L, Wang F, Hogan B, Que J. BMP signaling in the development of the mouse esophagus and forestomach. Development. 2010;137:4171-6 pubmed publisher
    ..Together, these findings suggest multiple roles for BMP signaling in the developing esophagus and forestomach. ..
  45. Xu Y, Li E, Han Y, Chen L, Xie Z. Differential expression of mRNAs encoding BMP/Smad pathway molecules in antral follicles of high- and low-fecundity Hu sheep. Anim Reprod Sci. 2010;120:47-55 pubmed publisher
  46. Miura S, Singh A, Mishina Y. Bmpr1a is required for proper migration of the AVE through regulation of Dkk1 expression in the pre-streak mouse embryo. Dev Biol. 2010;341:246-54 pubmed publisher
    ..Thus, our results suggest that BMP signaling regulates the expression patterns of Dkk1 for anterior migration of the AVE. ..
  47. Scott G, Ray M, Ward T, McCann K, Peddada S, Jiang F, et al. Abnormal glucose metabolism in heterozygous mutant mice for a type I receptor required for BMP signaling. Genesis. 2009;47:385-91 pubmed publisher
    ..Together, our data suggest that BMP signaling through BMPRIA plays an important role in glucose metabolism and possibly working through the GSIS pathway. ..
  48. Hong C, Yu P. Applications of small molecule BMP inhibitors in physiology and disease. Cytokine Growth Factor Rev. 2009;20:409-18 pubmed publisher
    ..We also discuss several potential applications for small molecule BMP inhibitors, including stem cell manipulation, and the therapeutic modification of bone remodeling, heterotopic ossification, and iron homeostasis. ..
  49. Kamiya N, Kobayashi T, Mochida Y, Yu P, Yamauchi M, Kronenberg H, et al. Wnt inhibitors Dkk1 and Sost are downstream targets of BMP signaling through the type IA receptor (BMPRIA) in osteoblasts. J Bone Miner Res. 2010;25:200-10 pubmed publisher
    ..This study highlights several interactions between BMP and Wnt signaling cascades in osteoblasts that may be amenable to therapeutic intervention for the modification of bone mass density. ..
  50. Guergnon J, Derewenda U, Edelson J, Brautigan D. Mapping of protein phosphatase-6 association with its SAPS domain regulatory subunit using a model of helical repeats. BMC Biochem. 2009;10:24 pubmed publisher
    ..The results advance understanding of how distinctive helical repeat subunits uniquely distribute and differentially regulate closely related Ser/Thr phosphatases. ..
  51. Kim S, Kim Y, Kim M, Kim D, Lee S, Chi S, et al. Comparative proteomic analysis of mouse melanoma cell line B16, a metastatic descendant B16F10, and B16 overexpressing the metastasis-associated tyrosine phosphatase PRL-3. Oncol Res. 2009;17:601-12 pubmed
    ..These proteins may play a causal role in PRL-3-mediated metastasis. These investigations open an avenue for the further characterization of the molecular mechanisms that underlie metastasis. ..
  52. Liu R, Ginn S, Lek M, North K, Alexander I, Little D, et al. Myoblast sensitivity and fibroblast insensitivity to osteogenic conversion by BMP-2 correlates with the expression of Bmpr-1a. BMC Musculoskelet Disord. 2009;10:51 pubmed publisher
    ..These data demonstrate the osteogenic sensitivity of muscle progenitors and provide a mechanistic insight into the variable response of different cell lineages to BMP-2. ..
  53. Chen D, Du S, Zhang H, Li H, Zhou J, Li Y, et al. Autocrine BMP4 signaling involves effect of cholesterol myristate on proliferation of mesenchymal stem cells. Steroids. 2009;74:1066-72 pubmed publisher
    ..Thus, this study is to provide evidence that autocrine BMP4 signaling involves effect of cholesterol myristate on MSCs proliferation. ..