Anthrax edema toxin modulates PKA- and CREB-dependent signaling in two phases.
<h4>Background</h4>Anthrax edema toxin (EdTx) is an adenylate cyclase which operates in the perinuclear region of host cells. However, the action of EdTx is poorly understood, especially at molecular level. The ability of EdTx to modulate cAMP-dependent signaling was studied in Jurkat T...
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Public Library of Science (PLoS)
2008-01-01
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| Series: | PLoS ONE |
| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18958164/?tool=EBI |
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| author | Andrea Puhar Federica Dal Molin Stéphanie Horvath Daniel Ladant Cesare Montecucco |
| author_facet | Andrea Puhar Federica Dal Molin Stéphanie Horvath Daniel Ladant Cesare Montecucco |
| author_sort | Andrea Puhar |
| collection | DOAJ |
| description | <h4>Background</h4>Anthrax edema toxin (EdTx) is an adenylate cyclase which operates in the perinuclear region of host cells. However, the action of EdTx is poorly understood, especially at molecular level. The ability of EdTx to modulate cAMP-dependent signaling was studied in Jurkat T cells and was compared with that of other cAMP-rising agents: Bordetella pertussis adenylate cyclase toxin, cholera toxin and forskolin.<h4>Methodology/principal findings</h4>EdTx caused a prolonged increase of the intracellular cAMP concentration. This led to nuclear translocation of the cAMP-dependent protein kinase (PKA) catalytic subunit, phosphorylation of cAMP response element binding protein (CREB) and expression of a reporter gene under control of the cAMP response element. Neither p90 ribosomal S6 kinase nor mitogen- and stress-activated kinase, which mediate CREB phosphorylation during T cell activation, were involved. The duration of phospho-CREB binding to chromatin correlated with the spatio-temporal rise of cAMP levels. Strikingly, EdTx pre-treated T cells were unresponsive to other stimuli involving CREB phosphorylation such as addition of forskolin or T cell receptor cross-linking.<h4>Conclusions/significance</h4>We concluded that, in a first intoxication phase, EdTx induces PKA-dependent signaling, which culminates in CREB phosphorylation and activation of gene transcription. Subsequently CREB phosphorylation is impaired and therefore T cells are not able to respond to cues involving CREB. The present data functionally link the perinuclear localization of EdTx to its intoxication mechanism, indicating that this is a specific feature of its intoxication mechanism. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T04:05:07Z |
| publishDate | 2008-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cb18ccb84866435bab3e205da3a56d6b2022-12-21T18:39:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01310e356410.1371/journal.pone.0003564Anthrax edema toxin modulates PKA- and CREB-dependent signaling in two phases.Andrea PuharFederica Dal MolinStéphanie HorvathDaniel LadantCesare Montecucco<h4>Background</h4>Anthrax edema toxin (EdTx) is an adenylate cyclase which operates in the perinuclear region of host cells. However, the action of EdTx is poorly understood, especially at molecular level. The ability of EdTx to modulate cAMP-dependent signaling was studied in Jurkat T cells and was compared with that of other cAMP-rising agents: Bordetella pertussis adenylate cyclase toxin, cholera toxin and forskolin.<h4>Methodology/principal findings</h4>EdTx caused a prolonged increase of the intracellular cAMP concentration. This led to nuclear translocation of the cAMP-dependent protein kinase (PKA) catalytic subunit, phosphorylation of cAMP response element binding protein (CREB) and expression of a reporter gene under control of the cAMP response element. Neither p90 ribosomal S6 kinase nor mitogen- and stress-activated kinase, which mediate CREB phosphorylation during T cell activation, were involved. The duration of phospho-CREB binding to chromatin correlated with the spatio-temporal rise of cAMP levels. Strikingly, EdTx pre-treated T cells were unresponsive to other stimuli involving CREB phosphorylation such as addition of forskolin or T cell receptor cross-linking.<h4>Conclusions/significance</h4>We concluded that, in a first intoxication phase, EdTx induces PKA-dependent signaling, which culminates in CREB phosphorylation and activation of gene transcription. Subsequently CREB phosphorylation is impaired and therefore T cells are not able to respond to cues involving CREB. The present data functionally link the perinuclear localization of EdTx to its intoxication mechanism, indicating that this is a specific feature of its intoxication mechanism.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18958164/?tool=EBI |
| spellingShingle | Andrea Puhar Federica Dal Molin Stéphanie Horvath Daniel Ladant Cesare Montecucco Anthrax edema toxin modulates PKA- and CREB-dependent signaling in two phases. PLoS ONE |
| title | Anthrax edema toxin modulates PKA- and CREB-dependent signaling in two phases. |
| title_full | Anthrax edema toxin modulates PKA- and CREB-dependent signaling in two phases. |
| title_fullStr | Anthrax edema toxin modulates PKA- and CREB-dependent signaling in two phases. |
| title_full_unstemmed | Anthrax edema toxin modulates PKA- and CREB-dependent signaling in two phases. |
| title_short | Anthrax edema toxin modulates PKA- and CREB-dependent signaling in two phases. |
| title_sort | anthrax edema toxin modulates pka and creb dependent signaling in two phases |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18958164/?tool=EBI |
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