PlumX Metrics
Embed PlumX Metrics

Formation of protein kinase Cε-Lck signaling modules confers cardioprotection

Journal of Clinical Investigation, ISSN: 0021-9738, Vol: 109, Issue: 4, Page: 499-507
2002
  • 142
    Citations
  • 0
    Usage
  • 32
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

Article Description

The ε isoform of protein kinase C (PKCε) is a member of the PKC family of serine/threonine kinases and plays a critical role in protection against ischemic injury in multiple organs. Functional proteomic analyses of PKCε signaling show that this isozyme forms multiprotein complexes in the heart; however, the precise signaling mechanisms whereby PKCε orchestrates cardioprotection are poorly understood. Here we report that Lck, a member of the Src family of tyrosine kinases, forms a functional signaling module with PKCε. In cardiac cells, PKCε interacts with, phosphorylates, and activates Lck. In vivo studies showed that cardioprotection elicited either by cardiac-specific transgenic activation of PKCε or by ischemic preconditioning enhances the formation of PKCε-Lck modules. Disruption of these modules, via ablation of the Lck gene, abrogated the infarct-sparing effects of these two forms of cardioprotection, indicating that the formation of PKCε-Lck signaling modules is required for the manifestation of a cardioprotective phenotype. These findings demonstrate, for the first time to our knowledge, that the assembly of a module (PKCε-Lck) is an obligatory step in the signal transduction that results in a specific phenotype. Thus, PKCε-Lck modules may serve as novel therapeutic targets for the prevention of ischemic injury.

Bibliographic Details

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know