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The cyclopentenone 15-deoxy-Δ 12,14 -prostaglandin J 2 binds to and activates H-Ras

2003; National Academy of Sciences; Volume: 100; Issue: 8 Linguagem: Inglês

10.1073/pnas.0735842100

1091-6490

José Luís Oliva, Dolores Pérez‐Sala, Antonio Castrillo, Natalia J. Martinez, F. Javier Cañada, Lisardo Boscá, José M. Rojas,

NF-κB Signaling Pathways

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.