The cyclopentenone 15-deoxy-Δ12,14-prostaglandin J2 binds to and activates H-Ras
JL Oliva, D Pérez-Sala, A Castrillo… - Proceedings of the …, 2003 - National Acad Sciences
Proceedings of the National Academy of Sciences, 2003•National Acad Sciences
The cyclopentenone 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2) induces cell
proliferation and mitogen-activated protein kinase activation. Here, we describe that these
effects are mediated by 15d-PGJ2-elicited H-Ras activation. We demonstrate that this
pathway is specific for H-Ras through the formation of a covalent adduct of 15d-PGJ2 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-PGJ2, whereas serum-elicited stimulation was not …
proliferation and mitogen-activated protein kinase activation. Here, we describe that these
effects are mediated by 15d-PGJ2-elicited H-Ras activation. We demonstrate that this
pathway is specific for H-Ras through the formation of a covalent adduct of 15d-PGJ2 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-PGJ2, whereas serum-elicited stimulation was not …
The cyclopentenone 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) induces cell proliferation and mitogen-activated protein kinase activation. Here, we describe that these effects are mediated by 15d-PGJ2-elicited H-Ras activation. We demonstrate that this pathway is specific for H-Ras through the formation of a covalent adduct of 15d-PGJ2 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-PGJ2, 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.
National Acad Sciences