Engagement of bone morphogenetic protein type IB receptor and Smad1 signaling by anti-Mullerian hormone and its type II receptor

Anti-Mullerian hormone induces the regression of fetal Mullerian ducts and inhibits the transcription of gonadal steroidogenic enzymes. It belongs to the transforming growth factor-p family whose members signal through a pair of serine/threonine kinase receptors and Smad effecters. Only the anti-Mul lerian hormone type II receptor has been identified. Our goal was to determ ine whether anti-Mullerian hormone could share a type I receptor with anoth er family member. Co-immunoprecipitation of known type I receptors with ant i-Mullerian hormone type II receptor clearly showed that the bone morphogen etic protein type LB receptor was the only cloned type I receptor interacti ng in a ligand-dependent manner with this type II receptor. Anti-Mullerian hormone also activates the bone morphogenetic protein-specific Smad1 pathwa y and the XVent2 reporter gene, an anti-Mullerian hormone type II receptor- dependent effect abrogated by a dominant negative version of bone morphogen etic protein type LB receptor. Reverse amplification experiments showed tha t bone morphogenetic protein type IB receptor is co-expressed with anti-Mul lerian hormone type II receptor in most anti-Mullerian hormone target tissu es. Our data support a model in which a ligand, anti-Mullerian hormone, gai ns access to a shared type I receptor and Smad1 system through a highly res tricted type II receptor.