β-adrenergic receptor signaling evokes the PKA-ASK axis in mature brown adipocytes.
Boosting energy expenditure by harnessing the activity of brown adipocytes is a promising strategy for combatting the global epidemic of obesity. Many studies have revealed that the β3-adrenergic receptor agonist is a potent activator of brown adipocytes, even in humans, and PKA and p38 MAPK have be...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0232645 |
| _version_ | 1819038031047294976 |
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| author | Kazuki Hattori Hiroaki Wakatsuki Chihiro Sakauchi Shotaro Furutani Sho Sugawara Tomohisa Hatta Tohru Natsume Hidenori Ichijo |
| author_facet | Kazuki Hattori Hiroaki Wakatsuki Chihiro Sakauchi Shotaro Furutani Sho Sugawara Tomohisa Hatta Tohru Natsume Hidenori Ichijo |
| author_sort | Kazuki Hattori |
| collection | DOAJ |
| description | Boosting energy expenditure by harnessing the activity of brown adipocytes is a promising strategy for combatting the global epidemic of obesity. Many studies have revealed that the β3-adrenergic receptor agonist is a potent activator of brown adipocytes, even in humans, and PKA and p38 MAPK have been demonstrated for regulating the transcription of a wide range of critical genes such as Ucp1. We previously revealed that the PKA-ASK1-p38 axis is activated in immature brown adipocytes and contributes to functional maturation. However, the downstream mechanisms of PKA that initiate the p38 MAPK cascade are still mostly unknown in mature brown adipocytes. Here, we identified the ASK family as a crucial signaling molecule bridging PKA and MAPK in mature brown adipocytes. Mechanistically, the phosphorylation of ASK1 at threonine 99 and serine 993 is critical in PKA-dependent ASK1 activation. Additionally, PKA also activates ASK2, which contributes to MAPK regulation. These lines of evidence provide new details for tailoring a βAR-dependent brown adipocyte activation strategy. |
| first_indexed | 2024-12-21T08:30:50Z |
| format | Article |
| id | doaj.art-66a2b155d113444383be97b2d121777d |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-21T08:30:50Z |
| publishDate | 2020-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-66a2b155d113444383be97b2d121777d2022-12-21T19:10:12ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-011510e023264510.1371/journal.pone.0232645β-adrenergic receptor signaling evokes the PKA-ASK axis in mature brown adipocytes.Kazuki HattoriHiroaki WakatsukiChihiro SakauchiShotaro FurutaniSho SugawaraTomohisa HattaTohru NatsumeHidenori IchijoBoosting energy expenditure by harnessing the activity of brown adipocytes is a promising strategy for combatting the global epidemic of obesity. Many studies have revealed that the β3-adrenergic receptor agonist is a potent activator of brown adipocytes, even in humans, and PKA and p38 MAPK have been demonstrated for regulating the transcription of a wide range of critical genes such as Ucp1. We previously revealed that the PKA-ASK1-p38 axis is activated in immature brown adipocytes and contributes to functional maturation. However, the downstream mechanisms of PKA that initiate the p38 MAPK cascade are still mostly unknown in mature brown adipocytes. Here, we identified the ASK family as a crucial signaling molecule bridging PKA and MAPK in mature brown adipocytes. Mechanistically, the phosphorylation of ASK1 at threonine 99 and serine 993 is critical in PKA-dependent ASK1 activation. Additionally, PKA also activates ASK2, which contributes to MAPK regulation. These lines of evidence provide new details for tailoring a βAR-dependent brown adipocyte activation strategy.https://doi.org/10.1371/journal.pone.0232645 |
| spellingShingle | Kazuki Hattori Hiroaki Wakatsuki Chihiro Sakauchi Shotaro Furutani Sho Sugawara Tomohisa Hatta Tohru Natsume Hidenori Ichijo β-adrenergic receptor signaling evokes the PKA-ASK axis in mature brown adipocytes. PLoS ONE |
| title | β-adrenergic receptor signaling evokes the PKA-ASK axis in mature brown adipocytes. |
| title_full | β-adrenergic receptor signaling evokes the PKA-ASK axis in mature brown adipocytes. |
| title_fullStr | β-adrenergic receptor signaling evokes the PKA-ASK axis in mature brown adipocytes. |
| title_full_unstemmed | β-adrenergic receptor signaling evokes the PKA-ASK axis in mature brown adipocytes. |
| title_short | β-adrenergic receptor signaling evokes the PKA-ASK axis in mature brown adipocytes. |
| title_sort | β adrenergic receptor signaling evokes the pka ask axis in mature brown adipocytes |
| url | https://doi.org/10.1371/journal.pone.0232645 |
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