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
- 142Citations
- 32Captures
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Metrics Details
- Citations142
- Citation Indexes142
- 142
- CrossRef101
- Captures32
- Readers32
- 19
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
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=0036177969&origin=inward; http://dx.doi.org/10.1172/jci0213200; http://dx.doi.org/10.1172/jci13200; http://www.ncbi.nlm.nih.gov/pubmed/11854322; http://www.jci.org/articles/view/13200; http://dx.doi.org/10.1172/jci200213200; https://dx.doi.org/10.1172/jci13200; https://www.jci.org/articles/view/13200; https://dx.doi.org/10.1172/jci0213200; https://dx.doi.org/10.1172/jci200213200
American Society for Clinical Investigation
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