Protein kinase C ε-Src modules direct signal transduction in nitric oxide-induced cardioprotection: Complex formation as a means for cardioprotective signaling

Thomas M. Vondriska, Jun Zhang, Changxu Song, Xian Liang Tang, Xinan Cao, Christopher P. Baines, Jason M. Pass, Shaoshan Wang, Roberto Bolli, Peipei Ping

Research output: Contribution to journalArticle

Abstract

An essential role for protein kinase C ε (PKCε) has been shown in multiple forms of cardioprotection; however, there is a distinct paucity of information concerning the signaling architecture that is responsible for the manifestation of a protective phenotype. We and others have recently shown that signal transduction may proceed via the formation of signaling complexes (Circ Res. 2001;88:59-62). In order to understand if the assembly of multiprotein complexes is the manner by which signaling is conducted in cardioprotection, we designed a series of experiments to characterize the associations of Src tyrosine kinase with PKCε in a conscious rabbit model of nitric oxide (NO)-induced late preconditioning. Our data demonstrate that PKCε and Src can form functional signaling modules in vitro: PKCε interacts with Src; the association with PKCε activates Src; and adult cardiac cells receiving recombinant adenoviruses encoding PKCε exhibit increased Src activity. Furthermore, our results show that NO-induced late preconditioning involved PKCε-Src module formation and enhanced the enzymatic activity of PKCε-associated Src. Inhibition of PKC blocked cardioprotection, module formation, and PKCε-associated Src activity, providing direct evidence for a functional role of the PKCε-Src module in the orchestration of NO-induced cardioprotection in conscious rabbits.

Original languageEnglish (US)
Pages (from-to)1306-1313
Number of pages8
JournalCirculation research
Volume88
Issue number12
DOIs
StatePublished - Jun 22 2001

Keywords

  • Ischemic injury
  • Preconditioning
  • Protein-protein interactions
  • Proteomics

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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    Vondriska, T. M., Zhang, J., Song, C., Tang, X. L., Cao, X., Baines, C. P., Pass, J. M., Wang, S., Bolli, R., & Ping, P. (2001). Protein kinase C ε-Src modules direct signal transduction in nitric oxide-induced cardioprotection: Complex formation as a means for cardioprotective signaling. Circulation research, 88(12), 1306-1313. https://doi.org/10.1161/hh1201.092994