Genomes and Genes
bone morphogenetic protein receptors
Summary: A family of CELL SURFACE RECEPTORS that bind BONE MORPHOGENETIC PROTEINS. They are PROTEIN-SERINE-THREONINE KINASES that mediate SIGNAL TRANSDUCTION PATHWAYS through SMAD PROTEINS.
- Timmer J, Wang C, Niswander L. BMP signaling patterns the dorsal and intermediate neural tube via regulation of homeobox and helix-loop-helix transcription factors. Development. 2002;129:2459-72 pubmed..This evidence strongly suggests that BMPs are the key regulators of dorsal cell identity in the spinal neural tube. ..
- Chen D, Zhao M, Harris S, Mi Z. Signal transduction and biological functions of bone morphogenetic proteins. Front Biosci. 2004;9:349-58 pubmed..Tissue-specific knockout of a specific BMP ligand, a subtype of BMP receptors or a specific signaling molecule is required to further determine the specific role of a particular BMP ligand, receptor or signaling molecule. ..
- Akiyoshi T, Uchida K, Tateyama S. Expression of bone morphogenetic protein-6 and bone morphogenetic protein receptors in myoepithelial cells of canine mammary gland tumors. Vet Pathol. 2004;41:154-63 pubmed
- Zhou F, Leder P, Zuniga A, Dettenhofer M. Formin1 disruption confers oligodactylism and alters Bmp signaling. Hum Mol Genet. 2009;18:2472-82 pubmed publisher..Additionally, these studies show enhanced activity downstream of the Bmp receptor in cells where Fmn1 is perturbed, suggesting a role for Fmn1 in repression of Bmp signaling...
- Pera E, Ikeda A, Eivers E, De Robertis E. Integration of IGF, FGF, and anti-BMP signals via Smad1 phosphorylation in neural induction. Genes Dev. 2003;17:3023-8 pubmed..This hard-wired molecular mechanism at the level of the Smad1 transcription factor may help explain the opposing activities of IGF, FGF, and BMP signals not only in neural induction, but also in other aspects of vertebrate development. ..
- Zilberberg L, Ten Dijke P, Sakai L, Rifkin D. A rapid and sensitive bioassay to measure bone morphogenetic protein activity. BMC Cell Biol. 2007;8:41 pubmed..The assay is rapid (less than 24 hours) and can be used, as described in this paper, to measure BMP activity in complex solutions and in cell culture in a simple and efficient way. ..
- Miller A, Harvey S, Thies R, Olson M. Bone morphogenetic protein-9. An autocrine/paracrine cytokine in the liver. J Biol Chem. 2000;275:17937-45 pubmed..Our results depict BMP-9 as a potential autocrine/paracrine mediator in the hepatic reticuloendothelial system. ..
- Bragdon B, Moseychuk O, Saldanha S, King D, Julian J, Nohe A. Bone morphogenetic proteins: a critical review. Cell Signal. 2011;23:609-20 pubmed publisher..It also highlights areas in research that is lacking or contradictory. ..
- Miyazono K. Signal transduction by bone morphogenetic protein receptors: functional roles of Smad proteins. Bone. 1999;25:91-3 pubmed..Anti-Smads are induced by ligand stimulation, suggesting that they constitute a negative feedback loop in the signal transduction pathways of the TGF-beta superfamily. ..
- Nohno T, Ishikawa T, Saito T, Hosokawa K, Noji S, Wolsing D, et al. Identification of a human type II receptor for bone morphogenetic protein-4 that forms differential heteromeric complexes with bone morphogenetic protein type I receptors. J Biol Chem. 1995;270:22522-6 pubmed..Furthermore, a subpopulation of super-high affinity binding sites is formed in COS cells upon cotransfection only of BRK-2 + BRK-3, suggesting that the different heteromeric BMP receptor complexes have different signaling potential. ..
- Ishidou Y, Kitajima I, Obama H, Maruyama I, Murata F, Imamura T, et al. Enhanced expression of type I receptors for bone morphogenetic proteins during bone formation. J Bone Miner Res. 1995;10:1651-9 pubmed..The present data suggest that expression of BMP type I receptors is up-regulated during bone formation, and that they may play important roles in bone morphogenesis. ..
- Aström A, Jin D, Imamura T, Roijer E, Rosenzweig B, Miyazono K, et al. Chromosomal localization of three human genes encoding bone morphogenetic protein receptors. Mamm Genome. 1999;10:299-302 pubmed..Using somatic cell hybrid and FISH analyses, the BMPR1A, BMPR1B, and BMPR2 genes were assigned to 10q23, 4q22-24, and 2q33-34, respectively. A processed BMPR1A pseudogene was mapped to 6q23. ..
- Suzuki A, Thies R, Yamaji N, Song J, Wozney J, Murakami K, et al. A truncated bone morphogenetic protein receptor affects dorsal-ventral patterning in the early Xenopus embryo. Proc Natl Acad Sci U S A. 1994;91:10255-9 pubmed..These findings suggest that endogenous BMP-2 and BMP-4 are involved in the dorsal-ventral specification in the embryo and that ventral fate requires induction rather than resulting from an absence of dorsal specification. ..
- Heinecke K, Seher A, Schmitz W, Mueller T, Sebald W, Nickel J. Receptor oligomerization and beyond: a case study in bone morphogenetic proteins. BMC Biol. 2009;7:59 pubmed publisher..This indicates that despite prominent ligand receptor promiscuity a manifold of diverse signals might be generated in this receptor limited system. ..
- Wilkinson L, Gilbert T, Kinna G, Ruta L, Pennisi D, Kett M, et al. Crim1KST264/KST264 mice implicate Crim1 in the regulation of vascular endothelial growth factor-A activity during glomerular vascular development. J Am Soc Nephrol. 2007;18:1697-708 pubmed..This is the first in vivo demonstration of regulation of VEGF-A delivery and supports the hypothesis that Crim1 functions to regulate the release of growth factors from the cell of synthesis. ..
- Wordinger R, Clark A. Bone morphogenetic proteins and their receptors in the eye. Exp Biol Med (Maywood). 2007;232:979-92 pubmed..Second, we review BMP and BMP receptor expression during embryonic ocular development/ differentiation and in adult ocular tissues. Lastly, future research directions with respect to BMP, BMP receptors, and ocular tissues are suggested. ..
- Takeda K, Oida S, Ichijo H, Iimura T, Maruoka Y, Amagasa T, et al. Molecular cloning of rat bone morphogenetic protein (BMP) type IA receptor and its expression during ectopic bone formation induced by BMP. Biochem Biophys Res Commun. 1994;204:203-9 pubmed..Reverse transcriptase-polymerase chain reaction analysis revealed that BMPR-IA mRNA was highly expressed in the BMP-induced bone forming tissues throughout the stages tested. ..
- Rosen V. BMP and BMP inhibitors in bone. Ann N Y Acad Sci. 2006;1068:19-25 pubmed..Identification of BMP antagonists allows us to investigate their role in diseases that affect skeletal function, such as osteopenia and nonunion fracture, and may provide a novel therapeutic intervention point for treatment. ..
- Singh A, Morris R. The Yin and Yang of bone morphogenetic proteins in cancer. Cytokine Growth Factor Rev. 2010;21:299-313 pubmed publisher..On the other hand, BMPs can sometimes function as a tumor suppressor. Our report highlights these new roles in the pathogenesis of cancer that may suggest novel targets for therapeutic intervention. ..
- Yanagisawa J, Yanagi Y, Masuhiro Y, Suzawa M, Watanabe M, Kashiwagi K, et al. Convergence of transforming growth factor-beta and vitamin D signaling pathways on SMAD transcriptional coactivators. Science. 1999;283:1317-21 pubmed..Thus, Smad3 may mediate cross-talk between vitamin D and TGF-beta signaling pathways. ..
- Wilkinson L, Gilbert T, Sipos A, Toma I, Pennisi D, Peti Peterdi J, et al. Loss of renal microvascular integrity in postnatal Crim1 hypomorphic transgenic mice. Kidney Int. 2009;76:1161-71 pubmed publisher..Our study suggests that Crim1 is involved in endothelial maintenance and integrity and its loss contributes to a primary defect in the extraglomerular vasculature. ..
- Shibuya H, Iwata H, Masuyama N, Gotoh Y, Yamaguchi K, Irie K, et al. Role of TAK1 and TAB1 in BMP signaling in early Xenopus development. EMBO J. 1998;17:1019-28 pubmed..These results thus suggest that xTAK1 and xTAB1 function in the BMP signal transduction pathway in Xenopus embryos in a cooperative manner. ..
- Souchelnytskyi S, Nakayama T, Nakao A, Moren A, Heldin C, Christian J, et al. Physical and functional interaction of murine and Xenopus Smad7 with bone morphogenetic protein receptors and transforming growth factor-beta receptors. J Biol Chem. 1998;273:25364-70 pubmed..Our results are consistent with the possibility that the C-domain of antagonistic Smads is an effector domain whereas the N-domain may confer specificity for distinct signaling pathways. ..
- Gilboa L, Nohe A, Geissendörfer T, Sebald W, Henis Y, 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. 2000;11:1023-35 pubmed..This novel feature in the oligomerization mode of the BMP receptors allows higher variety and flexibility in their responses to various ligands as compared with the TGF-beta receptors. ..
- Yamaguchi K, Nagai S, Ninomiya Tsuji J, Nishita M, Tamai K, Irie K, et al. XIAP, a cellular member of the inhibitor of apoptosis protein family, links the receptors to TAB1-TAK1 in the BMP signaling pathway. EMBO J. 1999;18:179-87 pubmed..These results suggest that XIAP participates in the BMP signaling pathway as a positive regulator linking the BMP receptors and TAB1-TAK1. ..
- Zimmerman L, De Jesús Escobar J, Harland R. The Spemann organizer signal noggin binds and inactivates bone morphogenetic protein 4. Cell. 1996;86:599-606 pubmed..These data suggest that noggin secreted by the organizer patterns the embryo by interrupting BMP signaling. ..
- Nohe A, Keating E, Knaus P, Petersen N. Signal transduction of bone morphogenetic protein receptors. Cell Signal. 2004;16:291-9 pubmed..This article reviews the current state of BMP receptor signaling and provides a summary of the crosstalk of the BMP receptor pathway with other major signaling pathways. ..
- Li J, Yoon S, Hutton W. Effect of bone morphogenetic protein-2 (BMP-2) on matrix production, other BMPs, and BMP receptors in rat intervertebral disc cells. J Spinal Disord Tech. 2004;17:423-8 pubmed..BMP-2 also up-regulates mRNA expression for BMP-7 and TGFbeta but has no significant effect on the BMPRs. ..
- Miyazono K, Maeda S, Imamura T. BMP receptor signaling: transcriptional targets, regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev. 2005;16:251-63 pubmed..Moreover, recent findings have revealed that BMP pathways interact with other signaling pathways, and such signaling cross-talk plays pivotal roles in growth and differentiation of target cells. ..
- Kinna G, Kolle G, Carter A, Key B, Lieschke G, Perkins A, et al. Knockdown of zebrafish crim1 results in a bent tail phenotype with defects in somite and vascular development. Mech Dev. 2006;123:277-87 pubmed..Hence, the primary role of zebrafish crim1 is likely to be the regulation of somitic and vascular development. ..
- Sieber C, Kopf J, Hiepen C, Knaus P. Recent advances in BMP receptor signaling. Cytokine Growth Factor Rev. 2009;20:343-55 pubmed publisher..Examples of BMP action during development, but also physiological and pathophysiological conditions in the adult organism are presented. ..
- Piccirillo S, Reynolds B, Zanetti N, Lamorte G, Binda E, Broggi G, et al. Bone morphogenetic proteins inhibit the tumorigenic potential of human brain tumour-initiating cells. Nature. 2006;444:761-5 pubmed
- Hassel S, Schmitt S, Hartung A, Roth M, Nohe A, Petersen N, et al. Initiation of Smad-dependent and Smad-independent signaling via distinct BMP-receptor complexes. J Bone Joint Surg Am. 2003;85-A Suppl 3:44-51 pubmed..These data clearly demonstrate that it is critical to fully understand receptor oligomerization in order to estimate signaling outcome for distinct receptor and ligand mutants. ..
- Ihida Stansbury K, McKean D, Lane K, Loyd J, Wheeler L, Morrell N, et al. Tenascin-C is induced by mutated BMP type II receptors in familial forms of pulmonary arterial hypertension. Am J Physiol Lung Cell Mol Physiol. 2006;291:L694-702 pubmed..These studies define a novel signaling network relevant to PAH underscored by BMPR2 mutations. ..
- Babitt J, Zhang Y, Samad T, Xia Y, Tang J, Campagna J, et al. Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor. J Biol Chem. 2005;280:29820-7 pubmed..Finally, we demonstrate that BMP signaling occurs in neurons that express RGMa in vivo. These data are consistent with a role for RGMa as a BMP co-receptor. ..
- Dupont S, Zacchigna L, Cordenonsi M, Soligo S, Adorno M, Rugge M, et al. Germ-layer specification and control of cell growth by Ectodermin, a Smad4 ubiquitin ligase. Cell. 2005;121:87-99 pubmed..We propose that Ectodermin is a key switch in the control of TGF-beta gene responses during early embryonic development and cell proliferation. ..
- Nishitoh H, Ichijo H, Kimura M, Matsumoto T, Makishima F, Yamaguchi A, et al. Identification of type I and type II serine/threonine kinase receptors for growth/differentiation factor-5. J Biol Chem. 1996;271:21345-52 pubmed..These results suggest that BMPR-IB mediates certain signals for GDF-5 after forming the heteromeric complex with BMPR-II or ActR-II. ..
- Piccolo S, Sasai Y, Lu B, De Robertis E. Dorsoventral patterning in Xenopus: inhibition of ventral signals by direct binding of chordin to BMP-4. Cell. 1996;86:589-98 pubmed..We propose that the noncell-autonomous effects of Spemann's organizer on dorsoventral patterning are executed in part by diffusible signals that directly bind to and neutralize ventral BMPs during gastrulation. ..
- Reddi A. Bone morphogenetic proteins: an unconventional approach to isolation of first mammalian morphogens. Cytokine Growth Factor Rev. 1997;8:11-20 pubmed..The successful isolation of first mammalian morphogens has laid the foundation for the elucidation of molecular signalling during morphogenesis in bones and beyond. ..
- 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. ..
- Dewulf N, Verschueren K, Lonnoy O, Moren A, Grimsby S, Vande Spiegle K, et al. Distinct spatial and temporal expression patterns of two type I receptors for bone morphogenetic proteins during mouse embryogenesis. Endocrinology. 1995;136:2652-63 pubmed..In addition, the expression of these genes in many soft tissues suggests broader functions for BMPs in embryogenesis. ..
- Yamashita H, Shimizu A, Kato M, Nishitoh H, Ichijo H, Hanyu A, et al. Growth/differentiation factor-5 induces angiogenesis in vivo. Exp Cell Res. 1997;235:218-26 pubmed..These results suggest that GDF-5 is one of the molecules which induce angiogenesis in the bone formation process. ..
- Zhang D, Mehler M, Song Q, Kessler J. Development of bone morphogenetic protein receptors in the nervous system and possible roles in regulating trkC expression. J Neurosci. 1998;18:3314-26 pubmed
- Raida M, Clement J, Leek R, Ameri K, Bicknell R, Niederwieser D, et al. Bone morphogenetic protein 2 (BMP-2) and induction of tumor angiogenesis. J Cancer Res Clin Oncol. 2005;131:741-50 pubmed..We conclude that activation of the BMP pathway by BMP-2 can promote vascularization and might be involved in tumor angiogenesis possibly by stimulating the Id1 and p38 MAPK pathway. ..
- Yeh L, Tsai A, Lee J. Osteogenic protein-1 (OP-1, BMP-7) induces osteoblastic cell differentiation of the pluripotent mesenchymal cell line C2C12. J Cell Biochem. 2002;87:292-304 pubmed..OP-1 enhanced ActR-I mRNA expression and significantly elevated the mRNA expressions of BMP-1, BMP-4, BMP-5, GDF-6, and GDF-8. The present results indicate that OP-1 is a potent inducer of C2C12 differentiation into osteoblastic cells. ..
- Graff J, Thies R, Song J, Celeste A, Melton D. Studies with a Xenopus BMP receptor suggest that ventral mesoderm-inducing signals override dorsal signals in vivo. Cell. 1994;79:169-79 pubmed
- Jeffery T, Upton P, Trembath R, Morrell N. BMP4 inhibits proliferation and promotes myocyte differentiation of lung fibroblasts via Smad1 and JNK pathways. Am J Physiol Lung Cell Mol Physiol. 2005;288:L370-8 pubmed
- Nohe A, Hassel S, Ehrlich M, Neubauer F, Sebald W, Henis Y, et al. The mode of bone morphogenetic protein (BMP) receptor oligomerization determines different BMP-2 signaling pathways. J Biol Chem. 2002;277:5330-8 pubmed
- Gould S, Day M, Jones S, Dorai H. BMP-7 regulates chemokine, cytokine, and hemodynamic gene expression in proximal tubule cells. Kidney Int. 2002;61:51-60 pubmed..Taken together, these observations suggest that BMP-7 may be a novel therapeutic agent for kidney disorders involving inflammation and ischemic damage of PTEC. ..
- Kawakami Y, Ishikawa T, Shimabara M, Tanda N, Enomoto Iwamoto M, Iwamoto M, et al. BMP signaling during bone pattern determination in the developing limb. Development. 1996;122:3557-66 pubmed
- Ten Dijke P, Korchynskyi O, Valdimarsdottir G, Goumans M. Controlling cell fate by bone morphogenetic protein receptors. Mol Cell Endocrinol. 2003;211:105-13 pubmed..Furthermore, recent studies reveal an important effector function for Id1 in various BMP-induced biological responses. ..
- Rosenzweig B, Imamura T, Okadome T, Cox G, Yamashita H, ten Dijke P, et al. Cloning and characterization of a human type II receptor for bone morphogenetic proteins. Proc Natl Acad Sci U S A. 1995;92:7632-6 pubmed..Binding of OP-1/BMP-7 to BMPR-II was also observed in nontransfected cell lines. Moreover, a transcriptional activation signal was transduced by BMPR-II in the presence of type I receptors after stimulation by OP-1/BMP-7. ..