L. Gilboa et al., Bone morphogenetic protein receptor complexes on the surface of live cells: A new oligomerization mode for serine/threonine kinase receptors, MOL BIOL CE, 11(3), 2000, pp. 1023-1035
The bone morphogenetic proteins (BMPs) play important roles in embryogenesi
s and normal cell growth. The BMP receptors belong to the family of serine/
threonine kinase receptors, whose activation has been investigated intensiv
ely for the transforming growth factor-beta (TGF-beta) 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 patte
rn as the TGF-beta receptors. Here we demonstrate that the oligomerization
pattern of the BMP receptors is different and is more flexible and suscepti
ble to modulation by ligand. Using several complementary approaches, we inv
estigated 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 recept
or (BR-II). Coimmunoprecipitation studies detected the formation of heterom
eric and homomeric complexes among all the BMP receptor types even in the a
bsence of ligand. These complexes were also detected at the cell surface af
ter BMP-2 binding and cross-linking. Using antibody-mediated immunofluoresc
ence copatching of epitope-tagged receptors, we provide evidence in live ce
lls for preexisting heteromeric (BR-II/ BR-Ia and BR-II/BR-Ib) and homomeri
c (BR-II/BR-II, BR-Ia/BR-Ia, BR-Ib/BR-Ib, and also BR-Ia/BR-Ib) oligomers i
n the absence of ligand. BMP-2 binding significantly increased hetero- and
homo-oligomerization (except for the BR-II homo-oligomer, which binds ligan
d poorly in the absence of BR-I). In contrast to previous observations on T
GF-beta receptors, which were found to be fully homodimeric in the absence
of ligand, the BMP receptors show a much more flexible oligomerization patt
ern. This novel feature in the oligomerization mode of the BMP receptors al
lows higher variety and flexibility in their responses to various ligands a
s compared with the TGF-beta receptors.