The cyclopentenone 15-deoxy-delta 12,14-prostaglandin J2 binds to and activates H-Ras
The cyclopentenone 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) induces cell proliferation and mitogen-activated protein kinase activation. Here, we describe that these effects are mediated by 15d-PGJ(2)-elicited H-Ras activation. We demonstrate that this pathway is specific for H-Ras throu...
| Autores: | , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2003 |
| País: | España |
| Institución: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/26115 |
| Acceso en línea: | https://hdl.handle.net/20.500.12105/26115 |
| Access Level: | acceso abierto |
| Palabra clave: | Mitogen-activated protein kinase Cell proliferation Posttranslational modification 3T3 Cells Amino Acid Sequence Animals Binding Sites COS Cells Cell Division Cysteine Gene Expression Regulation Genes, ras In Vitro Techniques MAP Kinase Signaling System Mice Molecular Sequence Data Mutagenesis, Site-Directed Mutation Prostaglandin D2 Protein Binding Recombinant Proteins ras Proteins |
| Sumario: | The cyclopentenone 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) induces cell proliferation and mitogen-activated protein kinase activation. Here, we describe that these effects are mediated by 15d-PGJ(2)-elicited H-Ras activation. We demonstrate that this pathway is specific for H-Ras through the formation of a covalent adduct of 15d-PGJ(2) with Cys-184 of H-Ras, but not with N-Ras or K-Ras. Mutation of C184 inhibited H-Ras modification and activation by 15d-PGJ(2), whereas serum-elicited stimulation was not affected. These results describe a mechanism for the activation of the Ras signaling pathway, which results from the chemical modification of H-Ras by formation of a covalent adduct with cyclopentenone prostaglandins. |
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