Transforming growth factor-beta (TGF-beta) signaling is mediated by a compl
ex of type I (TBRI) and type II (TBRII) receptors. The type III receptor (T
BRIII) Lacks a recognizable signaling domain and has no clearly defined rol
e in TGF-beta signaling. Cardiac endothelial cells that undergo epithelial-
mesenchymal transformation express TBRIII, and here TBRIII-specific antiser
a were found to inhibit mesenchyme formation and migration in atrioventricu
lar cushion explants. Misexpression of TBRIII in nontransforming ventricula
r endothelial cells conferred transformation in response to TGF-beta 2. The
se results support a model where TBRIII localizes transformation in the hea
rt and plays an essential, nonredundant role in TGF-beta signaling.