Oliva-Martinez, Jose LuisPérez-Sala, DoloresCastrillo, AntonioMartinez, NataliaCañada, F JavierBoscá, LisardoRojas-Cabañeros, Jose Maria2025-01-232025-01-232003-04-15Oliva JL, Pérez-Sala D, Castrillo A, Martínez N, Cañada FJ, Boscá L, Rojas JM. The cyclopentenone 15-deoxy-delta 12,14-prostaglandin J2 binds to and activates H-Ras. Proc Natl Acad Sci U S A. 2003 Apr 15;100(8):4772-7.0027-8424https://pmc.ncbi.nlm.nih.gov/articles/PMC153631/https://hdl.handle.net/20.500.12105/26115The 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.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/Mitogen-activated protein kinaseCell proliferationPosttranslational modification3T3 CellsAmino Acid SequenceAnimalsBinding SitesCOS CellsCell DivisionCysteineGene Expression RegulationGenes, rasIn Vitro TechniquesMAP Kinase Signaling SystemMiceMolecular Sequence DataMutagenesis, Site-DirectedMutationProstaglandin D2Protein BindingRecombinant Proteinsras ProteinsAttribution-NonCommercial-NoDerivatives 4.0 International1268453510084722-477710.1073/pnas.07358421001091-6490Proceedings of the National Academy of Sciences of the United States of Americaopen access