2.50
Hdl Handle:
http://hdl.handle.net/10146/82634
Title:
Role of cAMP in mediating AHR signaling.
Authors:
Oesch-Bartlomowicz, Barbara; Oesch, Franz
Abstract:
Regulation of the nuclear import of many transcription factors represents a step in gene regulation which is crucial for a number of cellular processes. The aryl hydrocarbon receptor (AHR), a basic helix-loop-helix protein of the PAS (PER-ARNT-SIM) family of transcriptional regulators is a cytosol-associated and ligand-activated receptor. The environmental toxin dioxin binds with high affinity to AHR rendering it nuclear and leading to the activation of AHR sensitive genes. However, the fact, that the AHR mediates a large variety of physiological events without the involvement of any known exogenous ligand, including liver and vascular system development, maturation of the immune system, regulation of genes involved in cellular growth, cell differentiation and circadian rhythm, speaks for an important role of AHR in cell biology independent of the presence of an exogenous ligand. Different approaches were applied to study mechanism(s) which render AHR nuclear and design its function in absence of exogenous ligands. We found that AHR is sensitive to cAMP signaling mediated by cAMP-dependent protein kinase (PKA) which fundamentally differs from AHR signaling mediated by the exogenous ligand dioxin. It has been shown that PKA mediated signaling can be confined by compartmentalization of signaling components in microdomains conferring specificity to signaling by the ubiquitous second messenger cAMP. Moreover, A-kinase-anchoring proteins (AKAPs) and newly discovered cAMP receptors, Epac (exchange protein directly activated by cAMP), may give us a further chance to enter into new dimensions of cAMP signal transmissions that potentially may bring us closer to AHR physiology.
Citation:
Biochem. Pharmacol. 2009, 77 (4):627-641
Journal:
Biochemical pharmacology
Issue Date:
15-Feb-2009
URI:
http://hdl.handle.net/10146/82634
DOI:
10.1016/j.bcp.2008.10.017
PubMed ID:
19013136
Additional Links:
http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T4P-4TTMJN5-1&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=b9a62489fc91ec4c021c5dafaf235c04
Type:
Article
Language:
en
ISSN:
1873-2968
Sponsors:
The authors thank ECNIS (Environmental Cancer, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: Food Quality and Safety (Contract no. 513943) for financial support.
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorOesch-Bartlomowicz, Barbaraen
dc.contributor.authorOesch, Franzen
dc.date.accessioned2009-09-25T07:51:10Z-
dc.date.available2009-09-25T07:51:10Z-
dc.date.issued2009-02-15-
dc.identifier.citationBiochem. Pharmacol. 2009, 77 (4):627-641en
dc.identifier.issn1873-2968-
dc.identifier.pmid19013136-
dc.identifier.doi10.1016/j.bcp.2008.10.017-
dc.identifier.urihttp://hdl.handle.net/10146/82634-
dc.description.abstractRegulation of the nuclear import of many transcription factors represents a step in gene regulation which is crucial for a number of cellular processes. The aryl hydrocarbon receptor (AHR), a basic helix-loop-helix protein of the PAS (PER-ARNT-SIM) family of transcriptional regulators is a cytosol-associated and ligand-activated receptor. The environmental toxin dioxin binds with high affinity to AHR rendering it nuclear and leading to the activation of AHR sensitive genes. However, the fact, that the AHR mediates a large variety of physiological events without the involvement of any known exogenous ligand, including liver and vascular system development, maturation of the immune system, regulation of genes involved in cellular growth, cell differentiation and circadian rhythm, speaks for an important role of AHR in cell biology independent of the presence of an exogenous ligand. Different approaches were applied to study mechanism(s) which render AHR nuclear and design its function in absence of exogenous ligands. We found that AHR is sensitive to cAMP signaling mediated by cAMP-dependent protein kinase (PKA) which fundamentally differs from AHR signaling mediated by the exogenous ligand dioxin. It has been shown that PKA mediated signaling can be confined by compartmentalization of signaling components in microdomains conferring specificity to signaling by the ubiquitous second messenger cAMP. Moreover, A-kinase-anchoring proteins (AKAPs) and newly discovered cAMP receptors, Epac (exchange protein directly activated by cAMP), may give us a further chance to enter into new dimensions of cAMP signal transmissions that potentially may bring us closer to AHR physiology.en
dc.description.sponsorshipThe authors thank ECNIS (Environmental Cancer, Nutrition and Individual Susceptibility), a network of excellence operating within the European Union 6th Framework Program, Priority 5: Food Quality and Safety (Contract no. 513943) for financial support.en
dc.language.isoenen
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T4P-4TTMJN5-1&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&_docanchor=&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=b9a62489fc91ec4c021c5dafaf235c04en
dc.subjectAryl hydrocarbon receptoren
dc.subjectcyclic AMPen
dc.subjectProtein kinase Aen
dc.subjectNuclear translocationen
dc.subjectSignal transductionen
dc.subjectDioxin toxicityen
dc.subjectPhosphorylationen
dc.subject.meshAnimals-
dc.subject.meshCell Line-
dc.subject.meshCyclic AMP-
dc.subject.meshCyclic AMP-Dependent Protein Kinases-
dc.subject.meshCytochrome P-450 CYP1A1-
dc.subject.meshDioxins-
dc.subject.meshEnvironmental Pollutants-
dc.subject.meshHumans-
dc.subject.meshLigands-
dc.subject.meshProtein Transport-
dc.subject.meshReceptors, Aryl Hydrocarbon-
dc.subject.meshSignal Transduction-
dc.titleRole of cAMP in mediating AHR signaling.en
dc.typeArticleen
dc.identifier.journalBiochemical pharmacologyen

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