{"title":"Diseases caused by altered specificity of a protein kinase for its allosteric activators.","authors":"Philip Cohen, Tom Snelling","doi":"10.1016/j.tibs.2024.10.008","DOIUrl":null,"url":null,"abstract":"<p><p>Protein kinases regulate many intracellular processes, and their dysregulation causes cancers and other diseases. This review focuses on the atypical alpha-kinase 1 (ALPK1), which is activated in mammalian cells by nucleoside diphosphate heptoses (ADP-heptose, UDP-heptose, and CDP-heptose) produced by microbial pathogens but not by mammalian cells. Mutations in human ALPK1 cause ROSAH syndrome and spiradenoma, which result from an alteration in its specificity for nucleoside diphosphate heptoses, causing aberrant activation by mammalian nucleoside diphosphate sugars without microbial infection. These may be the first diseases caused by altered specificity of an enzyme for its allosteric activators and has suggested ways in which selective drugs could be developed to treat them without compromising the innate immune system.</p>","PeriodicalId":440,"journal":{"name":"Trends in Biochemical Sciences","volume":" ","pages":""},"PeriodicalIF":11.6000,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in Biochemical Sciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.tibs.2024.10.008","RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Protein kinases regulate many intracellular processes, and their dysregulation causes cancers and other diseases. This review focuses on the atypical alpha-kinase 1 (ALPK1), which is activated in mammalian cells by nucleoside diphosphate heptoses (ADP-heptose, UDP-heptose, and CDP-heptose) produced by microbial pathogens but not by mammalian cells. Mutations in human ALPK1 cause ROSAH syndrome and spiradenoma, which result from an alteration in its specificity for nucleoside diphosphate heptoses, causing aberrant activation by mammalian nucleoside diphosphate sugars without microbial infection. These may be the first diseases caused by altered specificity of an enzyme for its allosteric activators and has suggested ways in which selective drugs could be developed to treat them without compromising the innate immune system.
期刊介绍：
For over 40 years, Trends in Biochemical Sciences (TIBS) has been a leading publication keeping readers informed about recent advances in all areas of biochemistry and molecular biology. Through monthly, peer-reviewed issues, TIBS covers a wide range of topics, from traditional subjects like protein structure and function to emerging areas in signaling and metabolism. Articles are curated by the Editor and authored by top researchers in their fields, with a focus on moving beyond simple literature summaries to providing novel insights and perspectives. Each issue primarily features concise and timely Reviews and Opinions, supplemented by shorter articles including Spotlights, Forums, and Technology of the Month, as well as impactful pieces like Science & Society and Scientific Life articles.
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