| http://purl.uniprot.org/citations/22267736 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/22267736 | http://www.w3.org/2000/01/rdf-schema#comment | "Inhibin is a heterodimeric peptide hormone produced in the ovary that antagonizes activin signaling and FSH synthesis in the pituitary. The inhibin β-subunit interacts with the activin type II receptor (ActRII) to functionally antagonize activin. The inhibin α-subunit mature domain (N terminus) arose relatively early during the evolution of the hormone, and inhibin function is decreased by an antibody directed against the α-subunit N-terminal extension region or by deletion of the N-terminal region. We hypothesized that the α-subunit N-terminal extension region interacts with the activin type I receptor (ALK4) to antagonize activin signaling in the pituitary. Human or chicken free α-subunit inhibited activin signaling in a pituitary gonadotrope-derived cell line (LβT2) in a dose-dependent manner, whereas an N-terminal extension deletion mutant did not. An α-subunit N-terminal peptide, but not a control peptide, was able to inhibit activin A signaling and decrease activin-stimulated FSH synthesis. Biotinylated inhibin A, but not activin A, bound ALK4. Soluble ALK4-ECD bioneutralized human free α-subunit in LβT2 cells, but did not affect activin A function. Competitive binding ELISAs with N-terminal mutants and an N-terminal region peptide confirmed that this region is critical for direct interaction of the α-subunit with ALK4. These data expand our understanding of how endocrine inhibin achieves potent antagonism of local, constitutive activin action in the pituitary, through a combined mechanism of competitive binding of both ActRII and ALK4 by each subunit of the inhibin heterodimer, in conjunction with the co-receptor betaglycan, to block activin receptor-ligand binding, complex assembly, and downstream signaling."xsd:string |
| http://purl.uniprot.org/citations/22267736 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.m111.293381"xsd:string |
| http://purl.uniprot.org/citations/22267736 | http://purl.uniprot.org/core/author | "Zhu J."xsd:string |
| http://purl.uniprot.org/citations/22267736 | http://purl.uniprot.org/core/author | "Lin S.J."xsd:string |
| http://purl.uniprot.org/citations/22267736 | http://purl.uniprot.org/core/author | "Jardetzky T.S."xsd:string |
| http://purl.uniprot.org/citations/22267736 | http://purl.uniprot.org/core/author | "Zou C."xsd:string |
| http://purl.uniprot.org/citations/22267736 | http://purl.uniprot.org/core/author | "Woodruff T.K."xsd:string |
| http://purl.uniprot.org/citations/22267736 | http://purl.uniprot.org/core/author | "Makanji Y."xsd:string |
| http://purl.uniprot.org/citations/22267736 | http://purl.uniprot.org/core/date | "2012"xsd:gYear |
| http://purl.uniprot.org/citations/22267736 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/22267736 | http://purl.uniprot.org/core/pages | "8060-8070"xsd:string |
| http://purl.uniprot.org/citations/22267736 | http://purl.uniprot.org/core/title | "Inhibin alpha-subunit N terminus interacts with activin type IB receptor to disrupt activin signaling."xsd:string |
| http://purl.uniprot.org/citations/22267736 | http://purl.uniprot.org/core/volume | "287"xsd:string |
| http://purl.uniprot.org/citations/22267736 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/22267736 |
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