Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The mammalian acetylcholinesterase (ACHE) gene gives rise to diverse enzymatically active proteins with three different carboxyl termini. In the brain, the normally rare readthrough AChE-R monomer accumulates under embryonic development and in adults following psychological stress, head injury, or exposure to AChEs. In the prenatal developing cortex, its unique C-terminal peptide ARP associates with radial glial fibers supporting neuronal migration. In contrast, the major synaptic AChE-S variant appears in the migrating neurons themselves. Moreover, antisense suppression of AChE-R attenuates neuronal migration, allowing increased proliferation of neuronal progenitors. In the adult brain, neuronal AChE-R is either secreted or accumulates intraneuronally, where it interacts through ARP with the scaffold protein RACK1 and activated PKC-betaII. This associates with increased PKC-betaII activity, which shuttles to submembranal clusters (e.g., in hyperactivated hippocampal neurons). Cleavage yields the AChE-R-specific C-terminal peptide, including immunopositive ARP. Importantly, intrahippocampal injection of synthetic ARP was followed by its efficient neuronal penetration and retrograde transport into cortical and basal nuclei neurons. Moreover, ARP-injected mice presented increased stress-induced contextual fear, inhibitable by antisense suppression of AChE-R mRNA. Together, our findings point at the cleavable ARP peptide as a key regulator of neuronal development and plasticity and suggest its use as a drug target and/or research and therapeutic tool.
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PMID:ARP, the cleavable C-terminal peptide of "readthrough" acetylcholinesterase, promotes neuronal development and plasticity. 1669 Oct 12

This article reviews what our colleagues have found as to how ischemic injury or cell death develop in myocardium through Ca(2+)-dependent protease calpain and how compensatory responses evolve through activation of intracellular signaling molecules including PKC isoforms, MAP kinase family enzymes and PI3 kinase. We also addressed how restraint or other psychological stress evokes hypertension and cardiovascular responses in signaling molecules or genes. Unexpectedly, carbon monoxide protects heart and cardiogenic cells against ischemia-resperfusion injury. When I think back, the unresolved cases of autopsies provided ideas for experimental study, which then taught us how the other cases died.
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PMID:Pursuing enigmas on ischemic heart disease and sudden cardiac death. 1904 46