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An extranuclear locus of cAMP-dependent protein kinase action is necessary and sufficient for promotion of spiral ganglion neuronal survival by cAMP
DC Field | Value | Language |
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dc.contributor.author | 복진웅 | - |
dc.date.accessioned | 2015-07-15T17:17:07Z | - |
dc.date.available | 2015-07-15T17:17:07Z | - |
dc.date.issued | 2003 | - |
dc.identifier.issn | 0270-6474 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/114602 | - |
dc.description.abstract | We showed previously that cAMP is a survival-promoting stimulus for cultured postnatal rat spiral ganglion neurons (SGNs) and that depolarization promotes SGN survival in part via recruitment of cAMP signaling. We here investigate the subcellular locus of cAMP prosurvival signaling. Transfection of GPKI, a green fluorescent protein (GFP)-tagged cAMP-dependent protein kinase (PKA) inhibitor, inhibits the ability of the permeant cAMP analog cpt-cAMP [8-(4-chlorophenylthio)-cAMP] to promote survival, indicating that PKA activity is necessary. Transfection of GFP-tagged PKA (GPKA) is sufficient to promote SGN survival, but restriction of GPKA to the nucleus by addition of a nuclear localization signal (GPKAnls) almost completely abrogates its prosurvival effect. In contrast, GPKA targeted to the extranuclear cytoplasm by addition of a nuclear export signal (GPKAnes) promotes SGN survival as effectively as does GPKA. Moreover, GPKI targeted to the nucleus lacks inhibitory effect on SGN survival attributable to cpt-cAMP or depolarization. These data indicate an extranuclear target of PKA for promotion of neuronal survival. Consistent with this, we find that dominant-inhibitory CREB mutants inhibit the prosurvival effect of depolarization but not that of cpt-cAMP. SGN survival is compromised by overexpression of the proapoptotic regulator Bad, previously shown to be phosphorylated in the cytoplasm by PKA. This Bad-induced apoptosis is prevented by cpt-cAMP or by cotransfection of GPKA or of GPKAnes but not of GPKAnls. Thus, cAMP prevents SGN death through a cytoplasmic as opposed to nuclear action, and inactivation of Bad proapoptotic function is a mechanism by which PKA can prevent neuronal death. | - |
dc.description.statementOfResponsibility | open | - |
dc.format | application/pdf | - |
dc.relation.isPartOf | JOURNAL OF NEUROSCIENCE | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/2.0/kr/ | - |
dc.subject.MESH | Animals | - |
dc.subject.MESH | Apoptosis/drug effects | - |
dc.subject.MESH | Apoptosis/physiology | - |
dc.subject.MESH | Carrier Proteins/biosynthesis | - |
dc.subject.MESH | Carrier Proteins/genetics | - |
dc.subject.MESH | Carrier Proteins/pharmacology | - |
dc.subject.MESH | Catalytic Domain/genetics | - |
dc.subject.MESH | Cell Nucleus/enzymology* | - |
dc.subject.MESH | Cell Survival/drug effects | - |
dc.subject.MESH | Cell Survival/genetics | - |
dc.subject.MESH | Cells, Cultured | - |
dc.subject.MESH | Cyclic AMP/analogs & derivatives* | - |
dc.subject.MESH | Cyclic AMP/antagonists & inhibitors | - |
dc.subject.MESH | Cyclic AMP/pharmacology* | - |
dc.subject.MESH | Cyclic AMP Response Element-Binding Protein/metabolism | - |
dc.subject.MESH | Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors | - |
dc.subject.MESH | Cyclic AMP-Dependent Protein Kinases/genetics | - |
dc.subject.MESH | Cyclic AMP-Dependent Protein Kinases/metabolism* | - |
dc.subject.MESH | Cytoplasm/enzymology | - |
dc.subject.MESH | Enzyme Inhibitors/pharmacology | - |
dc.subject.MESH | Green Fluorescent Proteins | - |
dc.subject.MESH | Luminescent Proteins/genetics | - |
dc.subject.MESH | Neurons/cytology | - |
dc.subject.MESH | Neurons/drug effects | - |
dc.subject.MESH | Neurons/enzymology* | - |
dc.subject.MESH | Nuclear Localization Signals/genetics | - |
dc.subject.MESH | Nuclear Localization Signals/physiology | - |
dc.subject.MESH | Phosphorylation/drug effects | - |
dc.subject.MESH | Rats | - |
dc.subject.MESH | Recombinant Fusion Proteins/genetics | - |
dc.subject.MESH | Recombinant Fusion Proteins/metabolism | - |
dc.subject.MESH | Recombinant Fusion Proteins/pharmacology | - |
dc.subject.MESH | Signal Transduction/physiology | - |
dc.subject.MESH | Spiral Ganglion/cytology | - |
dc.subject.MESH | Spiral Ganglion/drug effects | - |
dc.subject.MESH | Spiral Ganglion/enzymology* | - |
dc.subject.MESH | Thionucleotides/antagonists & inhibitors | - |
dc.subject.MESH | Thionucleotides/pharmacology | - |
dc.subject.MESH | Transfection | - |
dc.subject.MESH | bcl-Associated Death Protein | - |
dc.title | An extranuclear locus of cAMP-dependent protein kinase action is necessary and sufficient for promotion of spiral ganglion neuronal survival by cAMP | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Anatomy (해부학) | - |
dc.contributor.googleauthor | Jinwoong Bok | - |
dc.contributor.googleauthor | Xiang-Ming Zha | - |
dc.contributor.googleauthor | Steven H. Green | - |
dc.contributor.googleauthor | Yang-Sun Cho | - |
dc.admin.author | false | - |
dc.admin.mapping | false | - |
dc.contributor.localId | A01865 | - |
dc.relation.journalcode | J01633 | - |
dc.identifier.eissn | 1529-2401 | - |
dc.identifier.pmid | 12574406 | - |
dc.subject.keyword | membrane depolarization | - |
dc.subject.keyword | spiral ganglion neuron | - |
dc.subject.keyword | cell survival | - |
dc.subject.keyword | cAMP | - |
dc.subject.keyword | cAMP-dependent protein kinase | - |
dc.subject.keyword | PKA | - |
dc.subject.keyword | apoptosis | - |
dc.subject.keyword | Bad | - |
dc.subject.keyword | intracellular signal | - |
dc.subject.keyword | CREB | - |
dc.contributor.alternativeName | Bok, Jin Woong | - |
dc.contributor.affiliatedAuthor | Bok, Jin Woong | - |
dc.rights.accessRights | free | - |
dc.citation.volume | 23 | - |
dc.citation.number | 3 | - |
dc.citation.startPage | 777 | - |
dc.citation.endPage | 787 | - |
dc.identifier.bibliographicCitation | JOURNAL OF NEUROSCIENCE, Vol.23(3) : 777-787, 2003 | - |
dc.identifier.rimsid | 40056 | - |
dc.type.rims | ART | - |
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