The RGM/DRAGON family of BMP co-receptors

Cytokine and Growth Factor Reviews

Volumn 20, Issue 5-6, 2009, Pages 389-398

  Corradini, Elena ^a   Babitt, Jodie L ^a   Lin, Herbert Y ^a  

^a Center for Systems Biology   (United States)

Author keywords

BMP; DRAGON; HJV; Receptors; RGM

Indexed keywords

ACTIVIN RECEPTOR LIKE KINASE 1; BONE MORPHOGENETIC PROTEIN; BONE MORPHOGENETIC PROTEIN RECEPTOR; BONE MORPHOGENETIC PROTEIN RECEPTOR 1; BONE MORPHOGENETIC PROTEIN RECEPTOR 1A; BONE MORPHOGENETIC PROTEIN RECEPTOR 1B; BONE MORPHOGENETIC PROTEIN RECEPTOR 2; ENDOGLIN; HEMOJUVELIN; MEMBRANE PROTEIN; REPULSIVE GUIDANCE MOLECULE; SMAD PROTEIN; TRANSFORMING GROWTH FACTOR BETA RECEPTOR 1; UNCLASSIFIED DRUG;

BRAIN ISCHEMIA; CELL ACTIVITY; CELL MATURATION; GLAUCOMA; HEMOCHROMATOSIS; HISTOGENESIS; HUMAN; INFLAMMATION; NEURAL TUBE DEFECT; NONHUMAN; PATHOPHYSIOLOGY; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN FAMILY; PROTEIN FUNCTION; PROTEIN STRUCTURE; RECEPTOR UPREGULATION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; SPINAL CORD INJURY; TRAUMATIC BRAIN INJURY;

ANIMALS; BONE MORPHOGENETIC PROTEIN RECEPTORS; BONE MORPHOGENETIC PROTEINS; HUMANS; MEMBRANE PROTEINS; MODELS, BIOLOGICAL; NERVE TISSUE PROTEINS; PROTEIN BINDING; SIGNAL TRANSDUCTION;

EID: 70849085415     PISSN: 13596101     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.cytogfr.2009.10.008     Document Type: Review

References (102)

1. Miyazawa K., Shinozaki M., Hara T., Furuya T., and Miyazono K. Two major Smad pathways in TGF-beta superfamily signalling. Genes Cells 7 (2002) 1191-1204 Review
2. Shi Y., and Massagué J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113 (2003) 685-700 [review]
3. Welt C., Sidis Y., Keutmann H., and Schneyer A. Activins, inhibins, and follistatins: from endocrinology to signaling A paradigm for the new millennium. Exp Biol Med 227 (2002) 724-752 [review]
4. Weiskirchen R., Meurer S.K., Gressner O.A., Herrmann J., Borkham-Kamphorst E., and Gressner A.M. BMP-7 as antagonist of organ fibrosis. Front Biosci 14 (2009) 4992-5012
5. Zhao G.Q. Consequences of knocking out BMP signaling in the mouse. Genesis 35 (2003) 43-56 [review]
6. Chen D., Zhao M., and Mundy G.R. Bone Morphogenetic Proteins. Growth Factors 22 (2004) 233-241 [review]
7. Urist M.R. Bone formation by autoinduction. Science 150 (1965) 893-899
8. Wozney J.M., Rosen V., Celeste A.J., Mitsock L.M., Whitters M.J., Kriz R.W., et al. Novel regulators of bone formation: molecular clones and activities. Science 242 (1988) 1528-1534
9. David L., Feige J.J., and Bailly S. Emerging role of bone morphogenetic proteins in angiogenesis. Cytokine Growth Factor Rev 20 (2009) 203-212 [review]
10. Babitt J.L., Huang F.W., Wrighting D.M., Xia Y., Sidis Y., Samad T.A., et al. Bone morphogenetic protein signaling by hemojuvelin regulates hepcidin expression. Nat Genet 38 (2006) 531-539
11. Babitt J.L., Huang F.W., Xia Y., Sidis Y., Andrews N.C., and Lin H.Y. Modulation of bone morphogenetic protein signaling in vivo regulates systemic iron balance. J Clin Invest 117 (2007) 1933-1939
12. Caperuto L.C., Anhê G.F., Cambiaghi T.D., Akamine E.H., do Carmo Buonfiglio D., Cipolla-Neto J., et al. Modulation of bone morphogenetic protein-9 expression and processing by insulin, glucose, and glucocorticoids: possible candidate for hepatic insulin-sensitizing substance. Endocrinology 149 (2008) 6326-6335
13. Scott G.J., Ray M.K., Ward T., McCann K., Peddada S., Jiang F.X., et al. Abnormal glucose metabolism in heterozygous mutant mice for a type I receptor required for BMP signaling. Genesis 47 (2009) 385-391
14. Hardwick J.C., Kodach L.L., Offerhaus G.J., and van den Brink G.R. Bone morphogenetic protein signalling in colorectal cancer. Nat Rev Cancer 8 (2008) 806-812 [review]
15. Rosendahl A., Pardali E., Speletas M., Ten Dijke P., Heldin C.H., and Sideras P. Activation of bone morphogenetic protein/Smad signaling in bronchial epithelial cells during airway inflammation. Am J Respir Cell Mol Biol 27 (2002) 160-169
16. Gould S.E., Day M., Jones S.S., and Dorai H. BMP-7 regulates chemokine, cytokine, and hemodynamic gene expression in proximal tubule cells. Kidney Int 61 (2002) 51-60
17. Miyazono K., ten Dijke P., and Heldin C.H. TGF-beta signaling by Smad proteins. Adv Immunol 75 (2000) 115-157 [review]
18. Nohe A., Keating E., Knaus P., and Petersen N.O. Signal transduction of bone morphogenetic protein receptors. Cell Signal 16 (2004) 291-299 [review]
19. Moustakas A., and Heldin C.H. Non-SMAD TGF-beta signals. J Cell Sci 118 (2005) 3573-3584 [review]
20. Guo X., and Wang X.F. Signaling cross-talk between TGF-β/BMP and other pathways. Cell Res 19 (2009) 71-88 [review]
21. Oh S.P., Seki T., Goss K.A., Imamura T., Yi Y., Donahoe P.K., et al. Activin receptor-like kinase 1 modulates transforming growth factor-beta 1 signaling in the regulation of angiogenesis. Proc Natl Acad Sci USA 97 (2000) 2626-2631
22. Balemans W., and Van Hul W. Extracellular regulation of BMP signaling in vertebrates: a cocktail of modulators. Dev Biol 250 (2002) 231-250 [review]
23. Harland R.M. A twist on embryonic signaling. Nature 410 (2001) 423-424 [review]
24. Harrison C.A., Wiater E., Gray P.C., Greenwald J., Choe S., and Vale W. Modulation of Activin and BMP signaling. Mol Cell Endocrinol 225 (2004) 19-24 [review]
25. Yanagita M. BMP modulators regulate the function of BMP during body patterning and disease progression. Biofactors 35 (2009) 113-119 [review]
26. Blitz I.L., and Cho K.W. Finding partners: how BMPs select their targets. Dev Dyn 238 (2009) 1321-1331 [review]
27. Jin W., Takagi T., Kanesashi S.N., Kurahashi T., Nomura T., Harada J., et al. Schnurri-2 controls BMP-dependent adipogenesis via interaction with Smad proteins. Dev Cell 10 (2006) 461-471
28. Zhu H., Kavsak P., Abdollah S., Wrana J.L., and Thomsen G.H. A SMAD ubiquitin ligase targets the BMP pathway and affects embryonic pattern formation. Nature 400 (1999) 687-693
29. Lin E.A., Kong L., Bai X.H., Luan Y., and Liu C.J. miR-199a, a bone morphogenic protein 2-responsive MicroRNA, regulates chondrogenesis via direct targeting to SMAD1. J Biol Chem 284 (2009) 11326-11335
30. Rogler C.E., Levoci L., Ader T., Massimi A., Tchaikovskaya T., Norel R., et al. MicroRNA-23b cluster microRNAs regulate transforming growth factor-beta/bone morphogenetic protein signaling and liver stem cell differentiation by targeting SMADs. Hepatology March (2009) [Epub ahead of print]
31. Onichtchouk D., Chen Y.G., Dosch R., Gawantka V., Delius H., Massagué J., et al. Silencing of TGF-beta signalling by the pseudoreceptor BAMBI. Nature 401 (1999) 480-485
32. Cheifetz S., Bellon T., Cales C., Vera S., Bernabeu C., Massagué J., et al. Endoglin is a component of the transforming growth factor- receptor system in human endothelial cells. J Biol Chem 267 (1992) 19027-19030
33. Lebrin F., Goumans M.J., Jonker L., Carvalho R.L.C., Valdimarsdottir G., Thorikay M., et al. Endoglin promotes endothelial cell proliferation and TGF-/ALK1 signal transduction. EMBO 23 (2004) 4018-4028
34. Yeo C., and Whitman M. Nodal signals to SMADs through Cripto-dependent and Cripto-independent mechanisms. Mol Cell 7 (2001) 949-957
35. Yan Y.T., Liu J.J., Luo Y.E.C., Haltiwanger R.S., Abate-Shen C., and Shen M.M. Dual roles of Cripto as a ligand and coreceptor in the nodal signaling pathway. Mol Cell Biol 22 (2002) 4439-4449
36. Gray P.C., Harrison C.A., and Vale W. Cripto forms a complex with Activin and type II Activin receptors and can block Activin signaling. Proc Natl Acad Sci USA 100 (2003) 5193-5198
37. López-Casillas F., Wrana J.L., and Massagué J. Betaglycan presents ligand to the TGF beta signaling receptor. Cell 73 (1993) 1435-1444
38. Lewis K.A., Gray P.C., Blount A.L., MacConell L.A., Wiater E., Bilezikjian L.M., et al. Betaglycan binds inhibin and can mediate functional antagonism of Activin signalling. Nature 404 (2000) 411-414
39. Wiater E., Harrison C.A., Lewis K.A., Gray P.C., and Vale W.W. Identification of distinct inhibin and transforming growth factor beta-binding sites on betaglycan: functional separation of betaglycan co-receptor actions. J Biol Chem 281 (2006) 17011-17022
40. Kirkbride K.C., Townsend T.A., Bruinsma M.W., Barnett J.V., and Blobe G.C. Bone morphogenetic proteins signal through the transforming growth factor-beta type III receptor. J Biol Chem 283 (2008) 7628-7637
41. Babitt J.L., Zhang Y., Samad T.A., Xia Y., Tang J., Campagna J.A., et al. Repulsive guidance molecule (RGMa), a DRAGON homologue, is a bone morphogenetic protein co-receptor. J Biol Chem 280 (2005) 29820-29827
42. Samad T.A., Rebbapragada A., Bell E., Zhang Y., Sidis Y., Jeong S.J., et al. DRAGON, a bone morphogenetic protein co-receptor. J Biol Chem 280 (2005) 14122-14129
43. Monnier P.P., Sierra A., Macchi P., Deitinghoff L., Andersen J.S., Mann M., et al. RGM is a repulsive guidance molecule for retinal axons. Nature 419 (2002) 392-395
44. Camus L.M., and Lambert L.A. Molecular evolution of hemojuvelin and the repulsive guidance molecule family. J Mol Evol 65 (2007) 68-81
45. Mueller B.K., Yamashita T., Schaffar G., and Mueller R. The role of repulsive guidance molecules in the embryonic and adult vertebrate central nervous system. Philos Trans R Soc Lond B Biol Sci 361 (2006) 1513-1529 [review]
46. Zhang A.S., West Jr. A.P., Wyman A.E., Bjorkman P.J., and Enns C.A. Interaction of hemojuvelin with neogenin results in iron accumulation in human embryonic kidney 293 cells. J Biol Chem 280 (2005) 33885-33894
47. Kuninger D., Kuns-Hashimoto R., Kuzmickas R., and Rotwein P. Complex biosynthesis of the muscle-enriched iron regulator RGMc. J Cell Sci 119 (2006) 3273-3283
48. Xia Y., Sidis Y., Mukherjee A., Samad T.A., Brenner G., Woolf C.J., et al. Localization and action of Dragon (repulsive guidance molecule b), a novel bone morphogenetic protein coreceptor, throughout the reproductive axis. Endocrinology 146 (2005) 3614-3621
49. Samad T.A., Srinivasan A., Karchewski L.A., Jeong S.J., Campagna J.A., Ji R.R., et al. DRAGON: a member of the repulsive guidance molecule-related family of neuronal- and muscle-expressed membrane proteins is regulated by DRG11 and has neuronal adhesive properties. J Neurosci 24 (2004) 2027-2036
50. Rajagopalan S., Deitinghoff L., Davis D., Conrad S., Skutella T., Chedotal A., et al. Neogenin mediates the action of repulsive guidance molecule. Nat Cell Biol 6 (2004) 756-762
51. Schmidtmer J., and Engelkamp D. Isolation and expression pattern of three mouse homologues of chick Rgm. Gene Expr Patterns 4 (2004) 105-110
52. Niederkofler V., Salie R., Sigrist M., and Arber S. Repulsive guidance molecule (RGM) gene function is required for neural tube closure but not retinal topography in the mouse visual system. J Neurosci 24 (2004) 808-818
53. Wilson N.H., and Key B. Neogenin interacts with RGMa and netrin-1 to guide axons within the embryonic vertebrate forebrain. Dev Biol 296 (2006) 485-498
54. Brinks H., Conrad S., Vogt J., Oldekamp J., Sierra A., Deitinghoff L., et al. The repulsive guidance molecule RGMa is involved in the formation of afferent connections in the dentate gyrus. J Neurosci 24 (2004) 3862-3869
55. Hata K., Fujitani M., Yasuda Y., Doya H., Saito T., Yamagishi S., et al. RGMa inhibition promotes axonal growth and recovery after spinal cord injury. J Cell Biol 173 (2006) 47-58
56. Schwab J.M., Conrad S., Monnier P.P., Julien S., Mueller B.K., and Schluesener H.J. Spinal cord injury-induced lesional expression of the repulsive guidance molecule (RGM). Eur J Neurosci 21 (2005) 1569-1576
57. Schwab J.M., Monnier P.P., Schluesener H.J., Conrad S., Beschorner R., Chen L., et al. Central nervous system injury-induced repulsive guidance molecule expression in the adult human brain. Arch Neurol 62 (2005) 1561-1568
58. Oldekamp J., Krämer N., Alvarez-Bolado G., and Skutella T. Expression pattern of the repulsive guidance molecules RGM A, B and C during mouse development. Gene Expr Patterns 4 (2004) 283-288
59. Metzger M., Conrad S., Alvarez-Bolado G., Skutella T., and Just L. Gene expression of the repulsive guidance molecules during development of the mouse intestine. Dev Dyn 234 1 (2005) 169-175
60. Matsunaga E., Tauszig-Delamasure S., Monnier P.P., Mueller B.K., Strittmatter S.M., and Mehlen P. RGM and its receptor neogenin regulate neuronal survival. Nat Cell Biol 6 (2004) 749-755
61. Matsunaga E., Nakamura H., and Chédotal A. Repulsive guidance molecule plays multiple roles in neuronal differentiation and axon guidance. J Neurosci 26 (2006) 6082-6088
62. Xia Y., Yu P.B., Sidis Y., Beppu H., Bloch K.D., Schneyer A.L., et al. Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein (BMP) type II receptors by BMP2 and BMP4. J Biol Chem 282 (2007) 18129-18140
63. Halbrooks P.J., Ding R., Wozney J.M., and Bain G. Role of RGM coreceptors in bone morphogenetic protein signaling. J Mol Signal 2 (2007) 4
64. Conrad S., Genth H., Hofmann F., Just I., and Skutella T.J. Neogenin-RGMa signaling at the growth cone is bone morphogenetic protein-independent and involves RhoA, ROCK, and PKC. Biol Chem 282 (2007) 16423-16433
65. Andriopoulos Jr. B., Corradini E., Xia Y., Faasse S.A., Chen S., Grgurevic L., et al. BMP6 is a key endogenous regulator of hepcidin expression and iron metabolism. Nat Genet 41 4 (2009) 482-487
66. Kanomata K., Kokabu S., Nojima J., Fukuda T., and Katagiri T. DRAGON, a GPI-anchored membrane protein, inhibits BMP signaling in C2C12 myoblasts. Genes Cells May (2009) [Epub ahead of print]
67. Schnichels S., Conrad S., Warstat K., Henke-Fahle S., Skutella T., Schraermeyer U., et al. Gene expression of the repulsive guidance molecules/neogenin in the developing and mature mouse visual system: C57BL/6J vs. the glaucoma model DBA/2J. Gene Expr Patterns 8 (2007) 1-11
68. Liu X., Hashimoto M., Horii H., Yamaguchi A., Naito K., and Yamashita T. Repulsive guidance molecule b inhibits neurite growth and is increased after spinal cord injury. Biochem Biophys Res Commun 382 (2009) 795-800
69. Papanikolaou G., Samuels M.E., Ludwig E.H., MacDonald M.L., Franchini P.L., Dubé M.P., et al. Mutations in HFE2 cause iron overload in chromosome 1q-linked juvenile hemochromatosis. Nat Genet 36 (2004) 77-82
70. Lee P.L., Beutler E., Rao S.V., and Barton J.C. Genetic abnormalities and juvenile hemochromatosis: mutations of the HJV gene encoding hemojuvelin. Blood 103 (2004) 4669-4671
71. Pietrangelo A. Hemochromatosis: an endocrine liver disease. Hepatology 46 (2007) 1291-1301 [review]
72. Rodriguez Martinez A., Niemelä O., and Parkkila S. Hepatic and extrahepatic expression of the new iron regulatory protein hemojuvelin. Haematologica 89 (2004) 1441-1445
73. Rodriguez A., Pan P., and Parkkila S. Expression studies of neogenin and its ligand hemojuvelin in mouse tissues. J Histochem Cytochem 55 (2007) 85-96
74. Roetto A., Papanikolaou G., Politou M., Alberti F., Girelli D., Christakis J., et al. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat Genet 33 (2003) 21-22
75. Nemeth E., Tuttle M.S., Powelson J., Vaughn M.B., Donovan A., Ward D.M., et al. Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306 (2004) 2090-2093
76. Hentze M.W., Muckenthaler M.U., and Andrews N.C. Balancing acts; molecular control of mammalian iron metabolism. Cell 117 (2004) 285-297 [review]
77. Huang F.W., Pinkus J.L., Pinkus G.S., Fleming M.D., and Andrews N.C. A mouse model of juvenile hemochromatosis. J Clin Invest 115 (2005) 2187-2191
78. Niederkofler V., Salie R., and Arber S. Hemojuvelin is essential for dietary iron sensing, and its mutation leads to severe iron overload. J Clin Invest 115 (2005) 2180-2186
79. Xia Y., Babitt J.L., Sidis Y., Chung R.T., and Lin H.Y. Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin. Blood 111 (2008) 5195-5204
80. Kuns-Hashimoto R., Kuninger D., Nili M., and Rotwein P. Selective binding of RGMc/hemojuvelin, a key protein in systemic iron metabolism, to BMP-2 and neogenin. Am J Physiol Cell Physiol 294 (2008) C994-C1003
81. Yang F., West Jr. A.P., Allendorph G.P., Choe S., and Bjorkman P.J. Neogenin interacts with hemojuvelin through its two membrane-proximal fibronectin type III domains. Biochemistry 47 (2008) 4237-4245
82. Truksa J., Peng H., Lee P., and Beutler E. Bone morphogenetic proteins 2, 4, and 9 stimulate murine hepcidin 1 expression independently of Hfe, transferrin receptor 2 (Tfr2), and IL-6. Proc Natl Acad Sci USA 103 (2006) 10289-10293
83. Truksa J., Peng H., Lee P., and Beutler E. Different regulatory elements are required for response of hepcidin to interleukin-6 and bone morphogenetic proteins 4 and 9. Br J Haematol 139 (2007) 138-147
84. Verga Falzacappa M.V., Casanovas G., Hentze M.W., and Muckenthaler M.U. A bone morphogenetic protein (BMP)-responsive element in the hepcidin promoter controls HFE2-mediated hepatic hepcidin expression and its response to IL-6 in cultured cells. J Mol Med 86 (2008) 531-540
85. Truksa J., Lee P., and Beutler E. Two BMP responsive elements, STAT, and bZIP/HNF4/COUP motifs of the hepcidin promoter are critical for BMP, SMAD1, and HJV responsiveness. Blood 113 (2009) 688-695
86. Casanovas G., Mleczko-Sanecka K., Altamura S., Hentze M.W., and Muckenthaler M.U. Bone morphogenetic protein (BMP)-responsive elements located in the proximal and distal hepcidin promoter are critical for its response to HJV/BMP/SMAD. J Mol Med 87 (2009) 471-480
87. Wang R.H., Li C., Xu X., Zheng Y., Xiao C., Zerfas P., et al. A role of SMAD4 in iron metabolism through the positive regulation of hepcidin expression. Cell Metab 2 (2005) 399-409
88. Meynard D., Kautz L., Darnaud V., Canonne-Hergaux F., Coppin H., and Roth M.P. Lack of the bone morphogenetic protein BMP6 induces massive iron overload. Nat Genet 41 (2009) 478-481
89. Kuninger D., Kuns-Hashimoto R., Nili M., and Rotwein P. BMC Pro-protein convertases control the maturation and processing of the iron-regulatory protein RGMc/hemojuvelin. Biochemistry 2 9 (2008) 9
90. Silvestri L., Pagani A., and Camaschella C. Furin-mediated release of soluble hemojuvelin: a new link between hypoxia and iron homeostasis. Blood 111 (2008) 924-931
91. Lin L., Nemeth E., Goodnough J.B., Thapa D.R., Gabayan V., and Ganz T. Soluble hemojuvelin is released by proprotein convertase-mediated cleavage at a conserved polybasic RNRR site. Blood Cells Mol Dis 40 (2008) 122-131
92. Silvestri L., Pagani A., Fazi C., Gerardi G., Levi S., Arosio P., et al. Defective targeting of hemojuvelin to plasma membrane is a common pathogenetic mechanism in juvenile hemochromatosis. Blood 09 (2007) 4503-4510
93. Lin L., Goldberg Y.P., and Ganz T. Competitive regulation of hepcidin mRNA by soluble and cell-associated hemojuvelin. Blood 106 (2005) 2884-2889
94. Zhang A.S., Anderson S.A., Meyers K.R., Hernandez C., Eisenstein R.S., and Enns C.A. Evidence that inhibition of hemojuvelin shedding in response to iron is mediated through neogenin. J Biol Chem 282 (2007) 12547-12556
95. Silvestri L., Pagani A., Nai A., De Domenico I., Kaplan J., and Camaschella C. The serine protease matriptase-2 (TMPRSS6) inhibits hepcidin activation by cleaving membrane hemojuvelin. Cell Metab 8 (2008) 502-511
96. Zhang A.S., Yang F., Wang J., Tsukamoto H., and Enns C.A. Hemojuvelin/neogenin interaction is required for bone morphogenic protein-4-induced hepcidin expression. J Biol Chem June (2009) [Epub ahead of print]
97. Finberg K.E., Heeney M.M., Campagna D.R., Aydinok Y., Pearson H.A., Hartman K.R., et al. Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA). Nat Genet 40 (2008) 569-571
98. Du X., She E., Gelbart T., Truksa J., Lee P., Xia Y., et al. The serine protease TMPRSS6 is required to sense iron deficiency. Science 320 (2008) 1088-1092
99. Folgueras A.R., de Lara F.M., Pendás A.M., Garabaya C., Rodríguez F., Astudillo A., et al. Membrane-bound serine protease matriptase-2 (Tmprss6) is an essential regulator of iron homeostasis. Blood 112 (2008) 2539-2545
100. Krijt J., Vokurka M., Chang K.T., and Necas E. Expression of Rgmc, the murine ortholog of hemojuvelin gene, is modulated by development and inflammation, but not by iron status or erythropoietin. Blood 104 (2004) 4308-4310
101. Galligan C.L., Baig E., Bykerk V., Keystone E.C., and Fish E.N. Distinctive gene expression signatures in rheumatoid arthritis synovial tissue fibroblast cells: correlates with disease activity. Genes Immun 8 (2007) 480-491
102. Yu P.B., Hong C.C., Sachidanandan C., Babitt J.L., Deng D.Y., Hoyng S.A., et al. Dorsomorphin inhibits BMP signals required for embryogenesis and iron metabolism. Nat Chem Biol 4 1 (2008) 33-41