This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Moser, M.
Right arrow Articles by Patterson, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Moser, M.
Right arrow Articles by Patterson, C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2003, p. 5664-5679, Vol. 23, No. 16
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.16.5664-5679.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

BMPER, a Novel Endothelial Cell Precursor-Derived Protein, Antagonizes Bone Morphogenetic Protein Signaling and Endothelial Cell Differentiation

Martin Moser,1,2,3,4 Olav Binder,1,5 Yaxu Wu,1,2,3,4 Julius Aitsebaomo,1,2,3,4 Rongqin Ren,1,2,3,4 Christoph Bode,6 Victoria L. Bautch,1,7 Frank L. Conlon,1,5 and Cam Patterson1,2,3,4*

Carolina Cardiovascular Biology Center,1 Departments of Medicine,2 Pharmacology,3 Cell and Developmental Biology,4 Genetics,5 Biology, University of North Carolina, Chapel Hill, North Carolina,7 Department of Cardiology, University of Freiburg, Freiburg, Germany6

Received 20 December 2002/ Returned for modification 3 March 2003/ Accepted 20 May 2003

The development of endothelial cell precursors is essential for vasculogenesis. We screened for differentially expressed transcripts in endothelial cell precursors in developing mouse embryoid bodies. We cloned a complete cDNA encoding a protein that contains an amino-terminal signal peptide, five cysteine-rich domains, a von Willebrand D domain, and a trypsin inhibitor domain. We termed this protein BMPER (bone morphogenetic protein [BMP]-binding endothelial cell precursor-derived regulator). BMPER is specifically expressed in flk-1-positive cells and parallels the time course of flk-1 induction in these cells. In situ hybridization in mouse embryos demonstrates dorsal midline staining and staining of the aorto-gonadal-mesonephric region, which is known to host vascular precursor cells. BMPER is a secreted protein that directly interacts with BMP2, BMP4, and BMP6 and antagonizes BMP4-dependent Smad5 activation. In Xenopus embryos, ventral injection of BMPER mRNA results in axis duplication and downregulation of the expression of Xvent-1 (downstream target of Smad signaling). In an embryoid body differentiation assay, BMP4-dependent differentiation of endothelial cells in embryoid bodies is also antagonized by BMPER. Taken together, our data indicate that BMPER is a novel BMP-binding protein that is expressed by endothelial cell precursors, has BMP-antagonizing activity, and may play a role in endothelial cell differentiation by modulating local BMP activity.

* Corresponding author. Mailing address: Carolina Cardiovascular Biology Center, University of North Carolina at Chapel Hill, 5.109C Neurosciences Building, Chapel Hill, NC 27599-7126. Phone: (919) 843-6477. Fax: (919) 843-4585. E-mail: cpatters{at}med.unc.edu.

Molecular and Cellular Biology, August 2003, p. 5664-5679, Vol. 23, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.16.5664-5679.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Umulis, D., O'Connor, M. B., Blair, S. S. (2009). The extracellular regulation of bone morphogenetic protein signaling. Development 136: 3715-3728 [Abstract] [Full Text]  
  • Helbing, T., Volkmar, F., Goebel, U., Heinke, J., Diehl, P., Pahl, H. L., Bode, C., Patterson, C., Moser, M. (2009). Kruppel-like factor 15 regulates BMPER in endothelial cells. Cardiovasc Res 0: cvp314v2-cvp314 [Abstract] [Full Text]  
  • Jin, S.-W., Patterson, C. (2009). The Opening Act: Vasculogenesis and the Origins of Circulation. Arterioscler. Thromb. Vasc. Bio. 29: 623-629 [Abstract] [Full Text]  
  • Kelley, R., Ren, R., Pi, X., Wu, Y., Moreno, I., Willis, M., Moser, M., Ross, M., Podkowa, M., Attisano, L., Patterson, C. (2009). A concentration-dependent endocytic trap and sink mechanism converts Bmper from an activator to an inhibitor of Bmp signaling. JCB 184: 597-609 [Abstract] [Full Text]  
  • Heinke, J., Wehofsits, L., Zhou, Q., Zoeller, C., Baar, K.-M., Helbing, T., Laib, A., Augustin, H., Bode, C., Patterson, C., Moser, M. (2008). BMPER Is an Endothelial Cell Regulator and Controls Bone Morphogenetic Protein-4-Dependent Angiogenesis. Circ. Res. 103: 804-812 [Abstract] [Full Text]  
  • Harada, K., Ogai, A., Takahashi, T., Kitakaze, M., Matsubara, H., Oh, H. (2008). Crossveinless-2 Controls Bone Morphogenetic Protein Signaling during Early Cardiomyocyte Differentiation in P19 Cells. J. Biol. Chem. 283: 26705-26713 [Abstract] [Full Text]  
  • Jeong, J., Li, X., McEvilly, R. J., Rosenfeld, M. G., Lufkin, T., Rubenstein, J. L. R. (2008). Dlx genes pattern mammalian jaw primordium by regulating both lower jaw-specific and upper jaw-specific genetic programs. Development 135: 2905-2916 [Abstract] [Full Text]  
  • Wang, C., Faloon, P. W., Tan, Z., Lv, Y., Zhang, P., Ge, Y., Deng, H., Xiong, J.-W. (2007). Mouse lysocardiolipin acyltransferase controls the development of hematopoietic and endothelial lineages during in vitro embryonic stem-cell differentiation. Blood 110: 3601-3609 [Abstract] [Full Text]  
  • Ferguson, J. E. III, Wu, Y., Smith, K., Charles, P., Powers, K., Wang, H., Patterson, C. (2007). ASB4 Is a Hydroxylation Substrate of FIH and Promotes Vascular Differentiation via an Oxygen-Dependent Mechanism. Mol. Cell. Biol. 27: 6407-6419 [Abstract] [Full Text]  
  • Zhang, J.-L., Huang, Y., Qiu, L.-Y., Nickel, J., Sebald, W. (2007). von Willebrand Factor Type C Domain-containing Proteins Regulate Bone Morphogenetic Protein Signaling through Different Recognition Mechanisms. J. Biol. Chem. 282: 20002-20014 [Abstract] [Full Text]  
  • Silvestri, L., Pagani, A., Fazi, C., Gerardi, G., Levi, S., Arosio, P., Camaschella, C. (2007). Defective targeting of hemojuvelin to plasma membrane is a common pathogenetic mechanism in juvenile hemochromatosis. Blood 109: 4503-4510 [Abstract] [Full Text]  
  • Ren, R., Charles, P. C., Zhang, C., Wu, Y., Wang, H., Patterson, C. (2007). Gene expression profiles identify a role for cyclooxygenase 2-dependent prostanoid generation in BMP6-induced angiogenic responses. Blood 109: 2847-2853 [Abstract] [Full Text]  
  • Li, R. W., Meyer, M. J., Van Tassell, Curtis. P., Sonstegard, T. S., Connor, E. E., Van Amburgh, M. E., Boisclair, Y. R., Capuco, A. V. (2007). Identification of estrogen-responsive genes in the parenchyma and fat pad of the bovine mammary gland by microarray analysis. Physiol. Genomics 27: 42-53 [Abstract] [Full Text]  
  • Wang, H., Gilner, J. B., Bautch, V. L., Wang, D.-Z., Wainwright, B. J., Kirby, S. L., Patterson, C. (2007). Wnt2 Coordinates the Commitment of Mesoderm to Hematopoietic, Endothelial, and Cardiac Lineages in Embryoid Bodies. J. Biol. Chem. 282: 782-791 [Abstract] [Full Text]  
  • Ikeya, M., Kawada, M., Kiyonari, H., Sasai, N., Nakao, K., Furuta, Y., Sasai, Y. (2006). Essential pro-Bmp roles of crossveinless 2 in mouse organogenesis. Development 133: 4463-4473 [Abstract] [Full Text]  
  • Yao, Y., Zebboudj, A. F., Shao, E., Perez, M., Bostrom, K. (2006). Regulation of Bone Morphogenetic Protein-4 by Matrix GLA Protein in Vascular Endothelial Cells Involves Activin-like Kinase Receptor 1. J. Biol. Chem. 281: 33921-33930 [Abstract] [Full Text]  
  • Wang, H., Charles, P. C., Wu, Y., Ren, R., Pi, X., Moser, M., Barshishat-Kupper, M., Rubin, J. S., Perou, C., Bautch, V., Patterson, C. (2006). Gene Expression Profile Signatures Indicate a Role for Wnt Signaling in Endothelial Commitment From Embryonic Stem Cells. Circ. Res. 98: 1331-1339 [Abstract] [Full Text]  
  • Rentzsch, F., Zhang, J., Kramer, C., Sebald, W., Hammerschmidt, M. (2006). Crossveinless 2 is an essential positive feedback regulator of Bmp signaling during zebrafish gastrulation. Development 133: 801-811 [Abstract] [Full Text]  
  • O'Connor, M. B., Umulis, D., Othmer, H. G., Blair, S. S. (2006). Shaping BMP morphogen gradients in the Drosophila embryo and pupal wing. Development 133: 183-193 [Abstract] [Full Text]  
  • Ferguson, J.E. III, Kelley, R. W., Patterson, C. (2005). Mechanisms of Endothelial Differentiation in Embryonic Vasculogenesis. Arterioscler. Thromb. Vasc. Bio. 25: 2246-2254 [Abstract] [Full Text]  
  • Ferrari, N., Pfeffer, U., Dell'Eva, R., Ambrosini, C., Noonan, D. M., Albini, A. (2005). The Transforming Growth Factor-{beta} Family Members Bone Morphogenetic Protein-2 and Macrophage Inhibitory Cytokine-1 as Mediators of the Antiangiogenic Activity of N-(4-Hydroxyphenyl)Retinamide. Clin. Cancer Res. 11: 4610-4619 [Abstract] [Full Text]  
  • Juengel, J.L., McNatty, K.P. (2005). The role of proteins of the transforming growth factor-{beta} superfamily in the intraovarian regulation of follicular development. Hum Reprod Update 11: 144-161 [Abstract] [Full Text]  
  • Coles, E., Christiansen, J., Economou, A., Bronner-Fraser, M., Wilkinson, D. G. (2004). A vertebrate crossveinless 2 homologue modulates BMP activity and neural crest cell migration. Development 131: 5309-5317 [Abstract] [Full Text]  
  • Langenfeld, E. M., Langenfeld, J. (2004). Bone Morphogenetic Protein-2 Stimulates Angiogenesis in Developing Tumors. Mol Cancer Res 2: 141-149 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»