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Vol. 11, Issue 3, 1023-1035, March 2000
§
The bone morphogenetic proteins (BMPs) play important roles in
embryogenesis and normal cell growth. The BMP receptors belong to the
family of serine/threonine kinase receptors, whose activation has been
investigated intensively for the transforming growth factor-Department of Physiological Chemistry, Biocenter,
University of Würzburg, 97074 Würzburg, Germany; and
*Department of Neurobiochemistry, The George S. Wise Faculty of Life
Sciences, Tel Aviv University, Tel Aviv 69978, Israel
(TGF-) receptor subfamily. However, the interactions between the BMP
receptors, the composition of the active receptor complex, and the role
of the ligand in its formation have not yet been investigated and were
usually assumed to follow the same pattern as the TGF- receptors.
Here we demonstrate that the oligomerization pattern of the BMP
receptors is different and is more flexible and susceptible to
modulation by ligand. Using several complementary approaches, we
investigated the formation of homomeric and heteromeric complexes
between the two known BMP type I receptors (BR-Ia and BR-Ib) and the
BMP type II receptor (BR-II). Coimmunoprecipitation studies detected
the formation of heteromeric and homomeric complexes among all the BMP
receptor types even in the absence of ligand. These complexes were also
detected at the cell surface after BMP-2 binding and cross-linking.
Using antibody-mediated immunofluorescence copatching of epitope-tagged
receptors, we provide evidence in live cells for
preexisting heteromeric (BR-II/BR-Ia and BR-II/BR-Ib) and homomeric
(BR-II/BR-II, BR-Ia/ BR-Ia, BR-Ib/ BR-Ib, and also BR-Ia/ BR-Ib)
oligomers in the absence of ligand. BMP-2 binding significantly
increased hetero- and homo-oligomerization (except for the BR-II
homo-oligomer, which binds ligand poorly in the absence of BR-I). In
contrast to previous observations on TGF- receptors, which were
found to be fully homodimeric in the absence of ligand, the BMP
receptors show a much more flexible oligomerization pattern. 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- receptors.
These authors contributed equally to this work.
§
Corresponding author. E-mail address:
pknaus{at}biozentrum.uni-wuerzburg.de.
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