The cyclopentenone 15-deoxy-Δ 12,14 -prostaglandin J 2 binds to and activates H-Ras
Copyright policy )The cyclopentenone 15-deoxy-Δ 12,14 -prostaglandin J 2 binds to and activates H-Ras
The cyclopentenone 15-deoxy-Δ 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.
Binding Sites, MAP Kinase Signaling System, Prostaglandin D2, Molecular Sequence Data, 3T3 Cells, Mitogen-activated protein kinase, In Vitro Techniques, Recombinant Proteins, Mice, Genes, ras, Gene Expression Regulation, COS Cells, Mutation, Mutagenesis, Site-Directed, ras Proteins, Animals, Posttranslational modification, Amino Acid Sequence, Cysteine, Cell proliferation, Cell Division, Protein Binding
Binding Sites, MAP Kinase Signaling System, Prostaglandin D2, Molecular Sequence Data, 3T3 Cells, Mitogen-activated protein kinase, In Vitro Techniques, Recombinant Proteins, Mice, Genes, ras, Gene Expression Regulation, COS Cells, Mutation, Mutagenesis, Site-Directed, ras Proteins, Animals, Posttranslational modification, Amino Acid Sequence, Cysteine, Cell proliferation, Cell Division, Protein Binding
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