蛋白激酶对其异位激活剂的特异性改变导致的疾病。

IF 11.6 1区生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Trends in Biochemical Sciences Pub Date : 2024-11-22 DOI:10.1016/j.tibs.2024.10.008

Philip Cohen, Tom Snelling

{"title":"蛋白激酶对其异位激活剂的特异性改变导致的疾病。","authors":"Philip Cohen, Tom Snelling","doi":"10.1016/j.tibs.2024.10.008","DOIUrl":null,"url":null,"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.","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":"{\"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\":\"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.\",\"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}","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

摘要

蛋白激酶调控许多细胞内过程，它们的失调会导致癌症和其他疾病。非典型α-激酶1（ALPK1）在哺乳动物细胞中会被微生物病原体产生的核苷二磷酸庚糖（ADP-庚糖、UDP-庚糖和CDP-庚糖）激活，但不会被哺乳动物细胞激活。人类 ALPK1 基因突变会导致 ROSAH 综合征和螺旋体瘤，这是因为 ALPK1 对核苷酸二磷酸庚糖的特异性发生了改变，从而导致哺乳动物核苷酸二磷酸糖在没有微生物感染的情况下发生异常激活。这些可能是首例因酶对其异位激活剂的特异性改变而导致的疾病，并提出了在不损害先天免疫系统的情况下开发选择性药物治疗这些疾病的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

Diseases caused by altered specificity of a protein kinase for its allosteric activators.

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.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Trends in Biochemical Sciences 生物-生化与分子生物学

CiteScore

22.90

自引率

0.70%

发文量

148

审稿时长

6-12 weeks

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.