Nitric oxide (NO) induces nitration of protein kinase Cε (PKCε), facilitating PKCε translocation via enhanced PKCε-RACK2 interactions. A novel mechanism of no-triggered activation of PKCε

Zarema Balafanova, Roberto Bolli, Jun Zhang, Yuting Zheng, Jason M. Pass, Aruni Bhatnagar, Xian Liang Tang, Ouli Wang, Ernest Cardwell, Peipei Ping

Research output: Contribution to journalArticle

Abstract

Activation of protein kinase C (PKC) ε by nitric oxide (NO) has been implicated in the development of cardio-protection. However, the cellular mechanisms underlying the activation of PKCε by NO remain largely unknown. Nitration of protein tyrosine residues has been shown to alter functions of a variety of proteins, and NO-derived peroxynitrite is known as a strong nitrating agent. In this investigation, we demonstrate that NO donors promote translocation and activation of PKCε in an NO- and peroxynitrite-dependent fashion. NO induces peroxynitrite-mediated tyrosine nitration of PKCε in rabbit cardiomyocytes in vitro, and nitrotyrosine residues were also detected on PKCε in vivo in the rabbit myocardium preconditioned with NO donors. Furthermore, coimmunoprecipitation of PKCε and its receptor for activated C kinase, RACK2, illustrated a peroxynitrite-dependent increase in PKCε-RACK2 interactions in NO donor-treated cardiomyocytes. Moreover, using an enzyme-linked immunosorbent assay-based protein-protein interaction assay, PKCε proteins treated with the peroxynitrite donor SIN-1 exhibited enhanced binding to RACK2 in an acellular environment. Our data demonstrate that post-translational modification of PKCε by NO donors, namely nitration of PKCε, facilitates its interaction with RACK2 and promotes translocation and activation of PKCε. These findings offer a plausible novel mechanism by which NO activates the PKC signaling pathway.

Original languageEnglish (US)
Pages (from-to)15021-15027
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number17
DOIs
StatePublished - Apr 26 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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