Engagement of bone morphogenetic protein type IB receptor and Smad1 signaling by anti-Müllerian hormone and its type II receptor.
Anti-Müllerian hormone induces the regression of fetal Müllerian ducts and inhibits the transcription of gonadal steroidogenic enzymes. It belongs to the transforming growth factor-beta family whose members signal through a pair of serine/threonine kinase receptors and Smad effectors. Only the anti-Müllerian hormone type II receptor has been identified. Our goal was to determine whether anti-Müllerian hormone could share a type I receptor with another family member. Co-immunoprecipitation of known type I receptors with anti-Müllerian hormone type II receptor clearly showed that the bone morphogenetic protein type IB receptor was the only cloned type I receptor interacting in a ligand-dependent manner with this type II receptor. Anti-Müllerian hormone also activates the bone morphogenetic protein-specific Smad1 pathway and the XVent2 reporter gene, an anti-Müllerian hormone type II receptor-dependent effect abrogated by a dominant negative version of bone morphogenetic protein type IB receptor. Reverse amplification experiments showed that bone morphogenetic protein type IB receptor is co-expressed with anti-Müllerian hormone type II receptor in most anti-Müllerian hormone target tissues. Our data support a model in which a ligand, anti-Müllerian hormone, gains access to a shared type I receptor and Smad1 system through a highly restricted type II receptor.
Gouédard
L
L
Unité de Recherches sur l'Endocrinologie du Développement (INSERM), Ecole Normale Supérieure, Département de Biologie, 1 Rue Maurice-Arnoux, 92120 Montrouge, France.
Chen
Y G
YG
Thevenet
L
L
Racine
C
C
Borie
S
S
Lamarre
I
I
Josso
N
N
Massague
J
J
di Clemente
N
N
D000818:Animals; D054304:Anti-Mullerian Hormone; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II; D016466:CHO Cells; D002460:Cell Line; D006224:Cricetinae; D004268:DNA-Binding Proteins; D017930:Genes, Reporter; D006023:Glycoproteins; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011506:Proteins / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000502:physiology; D017978:Receptors, Growth Factor / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018000:Receptors, Peptide / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D051785:Smad Proteins; D051898:Smad1 Protein; D013735:Testicular Hormones / Q000494:pharmacology*; D015534:Trans-Activators; D014162:Transfection; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; D006023:Glycoproteins; D006131:Growth Inhibitors; D011506:Proteins; D011956:Receptors, Cell Surface; D017978:Receptors, Growth Factor; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; D011994:Recombinant Proteins; C497399:SMAD1 protein, human; D051785:Smad Proteins; D051898:Smad1 Protein; C497401:Smad1 protein, mouse; D013735:Testicular Hormones; D015534:Trans-Activators; C084621:anti-Mullerian hormone receptor; D054304:Anti-Mullerian Hormone; D017346:Protein Serine-Threonine Kinases; C498214:BMPR1B protein, human; C498218:BMPR2 protein, human; C498215:Bmpr1b protein, mouse; C498219:Bmpr2 protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I; D052006:Bone Morphogenetic Protein Receptors, Type II