A molecular redox switch on p21(ras). Structural basis for the nitric oxide-p21(ras) interaction

Harry M. Lander, David P. Hajjar, Barbara L. Hempstead, Urooj A. Mirza, Brian T. Chait, Sharon Campbell, Lawrence A. Quilliam

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430 Scopus citations


We have identified the site of molecular interaction between nitric oxide (NO) and p21(ras) responsible for initiation of signal transduction. We found that p21(ras) was singly S-nitrosylated and localized this modification to a fragment of p21(ras) containing Cys118. A mutant form of p21(ras), in which Cys118 was changed to a serine residue and termed p21(ras)C118S, was not S-nitrosylated. NO-related species stimulated guanine nucleotide exchange on wild-type p21(ras), resulting in an active form, but not on p2(ras)C118S. Furthermore, in contrast to parental Jurkat T cells, NO-related species did not stimulate mitogen-activated protein kinase activity in cells transfected with p21(ras)C118S. These data indicate that Cys118 is a critical site of redox regulation of p21(ras), and S-nitrosylation of this residue triggers guanine nucleotide exchange and downstream signaling.

Original languageEnglish (US)
Pages (from-to)4323-4326
Number of pages4
JournalJournal of Biological Chemistry
Issue number7
StatePublished - Feb 25 1997


ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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