Peroxynitrite treatment in vitro disables catalytic activity of recombinant p38 MAPK

Rose P. Webster, Stephen Macha, Diane Brockman, Leslie Myatt

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Protein tyrosine nitration is a post-translational modification occurring under conditions of oxidative stress in a number of diseases. The causative agent of tyrosine nitration is the potent prooxidant peroxynitrite that results from the interaction of nitric oxide and superoxide. We have previously demonstrated existence of nitrotyrosine in placenta from pregnancies complicated by preeclampsia, which suggested the possibility of the existence of nitrated proteins. Nitration of various proteins has been demonstrated to more commonly result in loss of protein function. Potential nitration of p38 MAPK, a critical signaling molecule has been suggested and also tentatively identified in certain in vivo systems. In this study we demonstrate for the first time nitration of recombinant p38 MAPK in vitro and an associated loss of its catalytic activity. LC-MS data identified tyrosine residues Y132, Y245 and Y258 to be nitrated. Nitration of these specific residues was deduced from the 45.0-Da change in mass that these residues exhibited that was consistent with the loss of a proton and addition of the nitro group.

Original languageEnglish (US)
Pages (from-to)4838-4844
Number of pages7
JournalProteomics
Volume6
Issue number17
DOIs
StatePublished - Sep 2006
Externally publishedYes

Fingerprint

Nitration
Peroxynitrous Acid
p38 Mitogen-Activated Protein Kinases
Catalyst activity
Tyrosine
Proteins
Post Translational Protein Processing
Pre-Eclampsia
Superoxides
Placenta
Protons
Nitric Oxide
Oxidative Stress
Oxidative stress
Pregnancy
In Vitro Techniques
Molecules

Keywords

  • Nitrotyrosine
  • p38 MAPK
  • Peroxynitrite
  • Preeclampsia

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

Cite this

Peroxynitrite treatment in vitro disables catalytic activity of recombinant p38 MAPK. / Webster, Rose P.; Macha, Stephen; Brockman, Diane; Myatt, Leslie.

In: Proteomics, Vol. 6, No. 17, 09.2006, p. 4838-4844.

Research output: Contribution to journalArticle

Webster, RP, Macha, S, Brockman, D & Myatt, L 2006, 'Peroxynitrite treatment in vitro disables catalytic activity of recombinant p38 MAPK', Proteomics, vol. 6, no. 17, pp. 4838-4844. https://doi.org/10.1002/pmic.200600176
Webster, Rose P. ; Macha, Stephen ; Brockman, Diane ; Myatt, Leslie. / Peroxynitrite treatment in vitro disables catalytic activity of recombinant p38 MAPK. In: Proteomics. 2006 ; Vol. 6, No. 17. pp. 4838-4844.
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