[PMID]: | 28747434 |
[Au] Autor: | Sallon C; Callebaut I; Boulay I; Fontaine J; Logeart-Avramoglou D; Henriquet C; Pugnière M; Cayla X; Monget P; Harichaux G; Labas V; Canepa S; Taragnat C |
[Ad] Endereço: | From the Unité Physiologie de la Reproduction et des Comportements, UMR85, Institut National de la Recherche Agronomique, CNRS, Institut Français du Cheval et de l'Equitation, Université de Tours, F-37380 Nouzilly, France. |
[Ti] Título: | Thrombospondin-1 (TSP-1), a new bone morphogenetic protein-2 and -4 (BMP-2/4) antagonist identified in pituitary cells. |
[So] Source: | J Biol Chem;292(37):15352-15368, 2017 09 15. |
[Is] ISSN: | 1083-351X |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | Bone morphogenetic proteins (BMPs) regulate diverse cellular responses during embryogenesis and in adulthood including cell differentiation, proliferation, and death in various tissues. In the adult pituitary, BMPs participate in the control of hormone secretion and cell proliferation, suggesting a potential endocrine/paracrine role for BMPs, but some of the mechanisms are unclear. Here, using a bioactivity test based on embryonic cells (C3H10T1/2) transfected with a BMP-responsive element, we sought to determine whether pituitary cells secrete BMPs or BMP antagonists. Interestingly, we found that pituitary-conditioned medium contains a factor that inhibits action of BMP-2 and -4. Combining surface plasmon resonance and high-resolution mass spectrometry helped pinpoint this factor as thrombospondin-1 (TSP-1). Surface plasmon resonance and co-immunoprecipitation confirmed that recombinant human TSP-1 can bind BMP-2 and -4 and antagonize their effects on C3H10T1/2 cells. Moreover, TSP-1 inhibited the action of serum BMPs. We also report that the von Willebrand type C domain of TSP-1 is likely responsible for this BMP-2/4-binding activity, an assertion based on sequence similarity that TSP-1 shares with the von Willebrand type C domain of Crossveinless 2 (CV-2), a BMP antagonist and member of the chordin family. In summary, we identified for the first time TSP-1 as a BMP-2/-4 antagonist and presented a structural basis for the physical interaction between TSP-1 and BMP-4. We propose that TSP-1 could regulate bioavailability of BMPs, either produced locally or reaching the pituitary via blood circulation. In conclusion, our findings provide new insights into the involvement of TSP-1 in the BMP-2/-4 mechanisms of action. |
[Mh] Termos MeSH primário: |
Proteína Morfogenética Óssea 2/antagonistas & inibidores Proteína Morfogenética Óssea 4/antagonistas & inibidores Modelos Moleculares Hipófise/secreção Elementos de Resposta Trombospondina 1/secreção
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[Mh] Termos MeSH secundário: |
Animais Animais Endogâmicos Proteína Morfogenética Óssea 2/sangue Proteína Morfogenética Óssea 2/genética Proteína Morfogenética Óssea 2/metabolismo Proteína Morfogenética Óssea 4/sangue Proteína Morfogenética Óssea 4/genética Proteína Morfogenética Óssea 4/metabolismo Linhagem Celular Células Cultivadas Biologia Computacional Feminino Genes Reporter Seres Humanos Camundongos Hipófise/citologia Hipófise/metabolismo Domínios e Motivos de Interação entre Proteínas Proteínas Recombinantes de Fusão/química Proteínas Recombinantes de Fusão/isolamento & purificação Proteínas Recombinantes de Fusão/metabolismo Proteínas Recombinantes/química Proteínas Recombinantes/metabolismo Homologia de Sequência de Aminoácidos Carneiro Doméstico Trombospondina 1/química Trombospondina 1/isolamento & purificação Trombospondina 1/metabolismo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (BMP2 protein, human); 0 (BMP4 protein, human); 0 (Bone Morphogenetic Protein 2); 0 (Bone Morphogenetic Protein 4); 0 (Recombinant Fusion Proteins); 0 (Recombinant Proteins); 0 (Thrombospondin 1); 0 (thrombospondin-1, human) |
[Em] Mês de entrada: | 1709 |
[Cu] Atualização por classe: | 171230 |
[Lr] Data última revisão:
| 171230 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 170728 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1074/jbc.M116.736207 |
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