Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

J. Cell Sci. 116 (16): 3277-3284

Research Article

Effect of the distribution and clustering of the type I A BMP receptor (ALK3) with the type II BMP receptor on the activation of signalling pathways

Anja Nohe1, Eleonora Keating1, T. Michael Underhill2, Petra Knaus3, and Nils O. Petersen1,*

1 Department of Chemistry, University of Western Ontario, London, N6A1B7, Canada
2 School of Dentistry, Faculty of Medicine and Dentistry, University of Western Ontario, London, N6A1B7, Canada
3 Department of Physiological Chemistry, University of Würzburg, 97074 Würzburg, Germany

* Author for correspondence (e-mail: petersen{at}

Accepted for publication 28 March 2003.

Abstract: Bone morphogenetic proteins (BMPs) play an important role during embryonic development, especially in chondrogenesis, osteogenesis, neurogenesis and hematopoiesis. There are over 19 BMPs known in mammalians, but only three BMP-type-I receptors and three BMP-type-II receptors are known so far to mediate these responses. Previous reports provide evidence to support that oligomerisation of BMP receptors influences the activation of the downstream BMP signalling pathways, the Smad or the p38 MAPK pathway. To further explore the importance of BMP receptor clustering in signalling, image correlation spectroscopy has been used to investigate the clustering and distribution of BMP receptors at the surface of the cell membrane. Here we demonstrate that the co-expression of the BMP-type-II receptor (BRII) influences the aggregation and the distribution of the BMP-type-Ia receptor (BRIa) in COS7 cells and in A431 cells. We also demonstrate that BMP-2 stimulation of the cells leads to a rearrangement of receptor complexes at the cell surface. Using A431 cells and limb bud-derived mesenchymal cells, we show that co-expression of the BRII and a constitutive active BRIa-ca is necessary for the activation of the Smad pathway. Importantly using a kinase-inactive BRII the rearrangement of BRIa is blocked. Together, these findings suggest that rearrangement of the receptors at the cell surface prior to forming preformed ligand independent complexes plays a critical role in activation of the Smad pathway. It also suggests further that the kinase activity of BRII is needed for signalling beyond the activation of BRIa at the GS domain.

Key Words: Image correlation spectroscopy • Fluorescence • BMP receptors • Receptor clusters • Smad pathway

Targeted gene delivery of BMPR2 attenuates pulmonary hypertension.
A. M. Reynolds, M. D. Holmes, S. M. Danilov, and P. N. Reynolds (2012)
Eur. Respir. J. 39, 329-343
   Abstract »    Full Text »    PDF »
Trapping of BMP receptors in distinct membrane domains inhibits their function in pulmonary arterial hypertension.
Y. Jiang, A. Nohe, B. Bragdon, C. Tian, N. Rudarakanchana, N. W. Morrell, and N. O. Petersen (2011)
Am J Physiol Lung Cell Mol Physiol 301, L218-L227
   Abstract »    Full Text »    PDF »
Image Correlation Spectroscopy.
A. Nohe and N. O Petersen (2008)
Science Signaling 1, pl7
   Abstract »    Full Text »    PDF »
Image Correlation Spectroscopy.
A. Nohe and N. O. Petersen (2007)
Sci. STKE 2007, pl7
   Abstract »    Full Text »    PDF »
Bone morphogenetic protein 2 and activin A synergistically stimulate follicle-stimulating hormone {beta} subunit transcription.
K. B Lee, V. Khivansara, M. M Santos, P. Lamba, T. Yuen, S. C Sealfon, and D. J Bernard (2007)
J. Mol. Endocrinol. 38, 315-330
   Abstract »    Full Text »    PDF »
Notch 1 Overexpression Inhibits Osteoblastogenesis by Suppressing Wnt/beta-Catenin but Not Bone Morphogenetic Protein Signaling.
V. Deregowski, E. Gazzerro, L. Priest, S. Rydziel, and E. Canalis (2006)
J. Biol. Chem. 281, 6203-6210
   Abstract »    Full Text »    PDF »
Dynamics and interaction of caveolin-1 isoforms with BMP-receptors.
A. Nohe, E. Keating, T. M. Underhill, P. Knaus, and N. O. Petersen (2005)
J. Cell Sci. 118, 643-650
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882