Protein Kinase C ε–Src Modules Direct Signal Transduction in Nitric Oxide–Induced Cardioprotection

Abstract

Abstract-An essential role for protein kinase C ⑀ (PKC⑀) 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

Sulindac confers high level ischemic protection to the heart through late preconditioning mechanisms

“…There is an extensive body of work implicating ROS dependent mechanisms in the triggering of delayed preconditioning by ischemia, exercise or other preconditioning stimuli (33)(34)(35)(36)(37). Following the trigger the next step in late preconditioning requires signaling through pathways that involve key protective kinases including PKC epsilon and PKC epsilon/Src containing modules (38,33). The ability of sulindac to induce preconditioning markers dependent on both PKC activity and ROS is strong evidence that sulindac is functioning as a chemical preconditioning agent.…”

Brevetoxin-induced phosphorylation of Pyk2 and Src in murine neocortical neurons involves distinct signaling pathways

“…It has been reported that PKC can directly bind to and activate Src (Moyers et al, 1993;Vondriska et al, 2001). Pyk2 activation was also found to be dependent on PKC activity.…”

Functional proteomic analysis of the myocardial PKCepsilon subproteome PKCepsilon-AKT-eNOS signaling modules and during.

“…Using whole cardiac cell Iysates (52, 142), our previous studies identified many molecular participants that comprise the cardiac PKCE signaling subproteome, however, information regarding the subcellular localization of PKCE associated proteins, which is essential to the mapping of this subproteome, is unknown. The formation and activation of specific PKCE signaling complexes at different subcellular compartments has been implicated to have significant functional consequences (12,172,173). Characterization of the subcellular distribution of PKCE complexes should provide key insights into the signaling mechanisms underlying the cardiac phenotypes observed in response to PKCE activation.…”

“…Moreover, specific modules are formed within subproteomes in response to different stimuli (145,160,172). Instead of attempting to Simultaneously examine all proteins in cardiac cells, we focus our research on characterization myocardial subproteomes that are critically involved in the development of ischemic injury and cardioprotection, especially the subproteomes of protein kinases associated with cardioprotection (136,142,172).…”

“…Moreover, specific modules are formed within subproteomes in response to different stimuli (145,160,172). Instead of attempting to Simultaneously examine all proteins in cardiac cells, we focus our research on characterization myocardial subproteomes that are critically involved in the development of ischemic injury and cardioprotection, especially the subproteomes of protein kinases associated with cardioprotection (136,142,172). Three aspects are important to characterize a subproteome: the identification of the proteins that compose the subproteome are classified according to their biological functions; the molecular architecture of the subproteome, the manner in which the subproteome is altered in different subcellular locations; and the dynamic modulation of the subproteome that underlies the development of a specific phenotype.…”