Madihah Hussain, Gonzalo S Tejeda, George S Baillie
{"title":"Posttranslational modifications of phosphodiesterase type 4 enzymes represent novel points for therapeutic targeting.","authors":"Madihah Hussain, Gonzalo S Tejeda, George S Baillie","doi":"10.1111/febs.70205","DOIUrl":null,"url":null,"abstract":"<p><p>Cyclic AMP is a second messenger that is produced in response to the activation of many G-protein-coupled receptors. As each receptor type is linked to a transient but distinct physiological outcome, the activation of cAMP effector proteins is highly compartmentalized by the action of phosphodiesterases (PDEs). Phosphodiesterase type 4 (PDE4) enzymes are expressed as 25 different isoforms, and the function of each protein is linked to its cellular location(s). Fine-tuning of cAMP dynamics in space and time is underpinned by PDE4 activity shifts or PDE4 translocations that are driven by posttranslational modifications. As 'omics' technology improves, we are now learning more about these PDE4 events, and we can link them to diseases where aberrant cAMP signaling is causative. Additionally, recent advances allow us to pinpoint specific PDE4 modifications with targeted therapies that will lessen the chances of side effects. This review charts all known PDE4 modifications and links them to innovative existing pharmaceutical concepts or possible future therapeutic developments.</p>","PeriodicalId":94226,"journal":{"name":"The FEBS journal","volume":" ","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"The FEBS journal","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1111/febs.70205","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Cyclic AMP is a second messenger that is produced in response to the activation of many G-protein-coupled receptors. As each receptor type is linked to a transient but distinct physiological outcome, the activation of cAMP effector proteins is highly compartmentalized by the action of phosphodiesterases (PDEs). Phosphodiesterase type 4 (PDE4) enzymes are expressed as 25 different isoforms, and the function of each protein is linked to its cellular location(s). Fine-tuning of cAMP dynamics in space and time is underpinned by PDE4 activity shifts or PDE4 translocations that are driven by posttranslational modifications. As 'omics' technology improves, we are now learning more about these PDE4 events, and we can link them to diseases where aberrant cAMP signaling is causative. Additionally, recent advances allow us to pinpoint specific PDE4 modifications with targeted therapies that will lessen the chances of side effects. This review charts all known PDE4 modifications and links them to innovative existing pharmaceutical concepts or possible future therapeutic developments.
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