TI  - Bone morphogenetic protein receptor complexes on the surface of live
      cells: a new oligomerization mode for serine/threonine kinase receptors.
PG  - 1023-35
AB  - 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 <prot>transforming growth factor-beta</prot>
      (<prot>TGF-beta</prot>) 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 <prot>TGF-beta</prot> 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 (<prot>BR-Ia</prot> and <prot>BR-Ib</prot>) and the <prot>BMP type II receptor</prot> (<prot>BR-II</prot>).
      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
      <prot>BMP-2</prot> binding and cross-linking. Using antibody-mediated
      immunofluorescence copatching of epitope-tagged receptors, we provide
      evidence in live cells for preexisting heteromeric ( <prot>BR-II</prot> / <prot>BR-Ia</prot>  and
       <prot>BR-II</prot> / <prot>BR-Ib</prot> ) and homomeric ( <prot>BR-II</prot> / <prot>BR-II</prot> ,   <prot>BR-Ia</prot> / <prot>BR-Ia</prot> ,  <prot>BR-Ib</prot> /  <prot>BR-Ib</prot> , and
      also  <prot>BR-Ia</prot> / <prot>BR-Ib</prot> ) oligomers in the absence of ligand. <prot>BMP-2</prot> binding
      significantly increased hetero- and homo-oligomerization (except for the
      <prot>BR-II</prot> homo-oligomer, which binds ligand poorly in the absence of <prot>BR-I</prot>). In
      contrast to previous observations on <prot>TGF-beta</prot> 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
      <prot>TGF-beta</prot> receptors.
AD  - Department of Neurobiochemistry, The George S. Wise Faculty of Life
