The cyclopentenone 15-deoxy-delta 12,14-prostaglandin J2 binds to and activates H-Ras.
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Oliva JL, Perez-Sala D, Castrillo A, Martinez N, Canada FJ, Bosca 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. Epub 2003 Apr 8.
- PubMed ID
- 12684535 [ View in PubMed]
- Abstract
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.