spacer gif spacer gif spacer gif spacer gif spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search    

The fully linked HTML version of this article has now been published.
JCS ePress online publication date 20 Feb 2007
doi: 10.1242/jcs.002949

This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
jcs.002949v1
120/6/964    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Scharpfenecker, M.
Right arrow Articles by ten Dijke, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Scharpfenecker, M.
Right arrow Articles by ten Dijke, P.

Research Article

BMP-9 signals via ALK1 and inhibits bFGF-induced endothelial cell proliferation and VEGF-stimulated angiogenesis


Marion Scharpfenecker, Maarten van Dinther, Zhen Liu, Rutger L. van Bezooijen, Qinghai Zhao, Laurie Pukac, Clemens W.G.M. Löwik, and Peter ten Dijke*
* Author for correspondence (e-mail: p.ten dijke{at}lumc.nl)

Genetic studies in mice and humans have shown that the transforming growth factor-{beta} (TGF-{beta}) type-I receptor activin receptor-like kinase 1 (ALK1) and its co-receptor endoglin play an important role in vascular development and angiogenesis. Here, we demonstrate that ALK1 is a signalling receptor for bone morphogenetic protein-9 (BMP-9) in endothelial cells (ECs). BMP-9 bound with high affinity to ALK1 and endoglin, and weakly to the type-I receptor ALK2 and to the BMP type-II receptor (BMPR-II) and activin type-II receptor (ActR-II) in transfected COS cells. Binding of BMP-9 to ALK2 was greatly facilitated when BMPR-II or ActR-II were co-expressed. Whereas BMP-9 predominantly bound to ALK1 and BMPR-II in ECs, it bound to ALK2 and BMPR-II in myoblasts. In addition, we observed binding of BMP-9 to ALK1 and endoglin in glioblastoma cells. BMP-9 activated Smad1 and/or Smad5, and induced ID1 protein and endoglin mRNA expression in ECs. Furthermore, BMP-9 was found to inhibit basic fibroblast growth factor (bFGF)-stimulated proliferation and migration of bovine aortic ECs (BAECs) and to block vascular endothelial growth factor (VEGF)-induced angiogenesis. Taken together, these results suggest that BMP-9 is a physiological ALK1 ligand that plays an important role in the regulation of angiogenesis.




This article has been cited by other articles:


Home page
 Circ. Res.Home page
L. David, C. Mallet, M. Keramidas, N. Lamande, J.-M. Gasc, S. Dupuis-Girod, H. Plauchu, J.-J. Feige, and S. Bailly
Bone Morphogenetic Protein-9 Is a Circulating Vascular Quiescence Factor
Circ. Res., April 25, 2008; 102(8): 914 - 922.
[Abstract] [Full Text] [PDF]

Home page
 Clin. Cancer Res.Home page
N. A. Dallas, S. Samuel, L. Xia, F. Fan, M. J. Gray, S. J. Lim, and L. M. Ellis
Endoglin (CD105): A Marker of Tumor Vasculature and Potential Target for Therapy
Clin. Cancer Res., April 1, 2008; 14(7): 1931 - 1937.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
M. T. Holderfield and C. C.W. Hughes
Crosstalk Between Vascular Endothelial Growth Factor, Notch, and Transforming Growth Factor-{beta} in Vascular Morphogenesis
Circ. Res., March 28, 2008; 102(6): 637 - 652.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
P. D. Upton, L. Long, R. C. Trembath, and N. W. Morrell
Functional Characterization of Bone Morphogenetic Protein Binding Sites and Smad1/5 Activation in Human Vascular Cells
Mol. Pharmacol., February 1, 2008; 73(2): 539 - 552.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. O. Park, Y. J. Lee, T. Seki, K.-H. Hong, N. Fliess, Z. Jiang, A. Park, X. Wu, V. Kaartinen, B. L. Roman, et al.
ALK5- and TGFBR2-independent role of ALK1 in the pathogenesis of hereditary hemorrhagic telangiectasia type 2
Blood, January 15, 2008; 111(2): 633 - 642.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
P. Brouillard and M. Vikkula
Genetic causes of vascular malformations
Hum. Mol. Genet., October 15, 2007; 16(R2): R140 - R149.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
L. Lin, E. V. Valore, E. Nemeth, J. B. Goodnough, V. Gabayan, and T. Ganz
Iron transferrin regulates hepcidin synthesis in primary hepatocyte culture through hemojuvelin and BMP2/4
Blood, September 15, 2007; 110(6): 2182 - 2189.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
D. Liu, J. Wang, B. Kinzel, M. Mueller, X. Mao, R. Valdez, Y. Liu, and E. Li
Dosage-dependent requirement of BMP type II receptor for maintenance of vascular integrity
Blood, September 1, 2007; 110(5): 1502 - 1510.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Goto, Y. Kamiya, T. Imamura, K. Miyazono, and K. Miyazawa
Selective Inhibitory Effects of Smad6 on Bone Morphogenetic Protein Type I Receptors
J. Biol. Chem., July 13, 2007; 282(28): 20603 - 20611.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2007