Gouédard L, Chen Y G, Thevenet L, Racine C, Borie S, Lamarre I, Josso N, Massague J, di Clemente N
Unité de Recherches sur l'Endocrinologie du Développement (INSERM), Ecole Normale Supérieure, Département de Biologie, 1 Rue Maurice-Arnoux, 92120 Montrouge, France.
J Biol Chem. 2000 Sep 8;275(36):27973-8. doi: 10.1074/jbc.M002704200.
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.
抗苗勒管激素可诱导胎儿苗勒管退化,并抑制性腺类固醇生成酶的转录。它属于转化生长因子-β家族,该家族成员通过一对丝氨酸/苏氨酸激酶受体和Smad效应器进行信号传导。目前仅鉴定出抗苗勒管激素II型受体。我们的目标是确定抗苗勒管激素是否能与另一个家族成员共用I型受体。已知的I型受体与抗苗勒管激素II型受体的共免疫沉淀结果清楚地表明,骨形态发生蛋白IB型受体是唯一以配体依赖方式与该II型受体相互作用的克隆I型受体。抗苗勒管激素还可激活骨形态发生蛋白特异性的Smad1信号通路以及XVent2报告基因,而骨形态发生蛋白IB型受体的显性负性形式可消除这种依赖抗苗勒管激素II型受体的效应。反向扩增实验表明,在大多数抗苗勒管激素靶组织中,骨形态发生蛋白IB型受体与抗苗勒管激素II型受体共表达。我们的数据支持这样一种模型,即配体抗苗勒管激素通过高度受限的II型受体与共用的I型受体和Smad1系统结合。