Beibei Wang, Mengge Cui, Huan Liu, Ming Sui, Xueyan Wu, Yu Liu, Bin Zhang
{"title":"Agrin/Dok-7-induced JPH2 phosphorylation in muscle cells is involved in AChR clustering.","authors":"Beibei Wang, Mengge Cui, Huan Liu, Ming Sui, Xueyan Wu, Yu Liu, Bin Zhang","doi":"10.1002/1873-3468.70050","DOIUrl":null,"url":null,"abstract":"<p><p>The neuromuscular junction (NMJ) performs the crucial function of controlling skeletal muscle contraction. NMJ formation depends on the Agrin/Lrp4/MuSK/Dok-7 signaling pathway. However, signaling downstream of Dok-7 remains incompletely understood. Here we used the phosphorylated iTRAQ technique to identify downstream molecules of Dok-7 in muscle cells. We found 16 Agrin/Dok-7-mediated serine/threonine phosphorylated proteins, and we validated the role of one phosphorylated protein, JPH2, in regulating AChR clustering. Our phosphoproteomics analysis sheds light on the underappreciated signaling network downstream of Agrin/Dok-7, thus providing new clues for understanding pathogenesis and developing treatment methods for neuromuscular diseases.</p>","PeriodicalId":12142,"journal":{"name":"FEBS Letters","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"FEBS Letters","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/1873-3468.70050","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
引用次数: 0
Abstract
The neuromuscular junction (NMJ) performs the crucial function of controlling skeletal muscle contraction. NMJ formation depends on the Agrin/Lrp4/MuSK/Dok-7 signaling pathway. However, signaling downstream of Dok-7 remains incompletely understood. Here we used the phosphorylated iTRAQ technique to identify downstream molecules of Dok-7 in muscle cells. We found 16 Agrin/Dok-7-mediated serine/threonine phosphorylated proteins, and we validated the role of one phosphorylated protein, JPH2, in regulating AChR clustering. Our phosphoproteomics analysis sheds light on the underappreciated signaling network downstream of Agrin/Dok-7, thus providing new clues for understanding pathogenesis and developing treatment methods for neuromuscular diseases.
神经肌肉接点（NMJ）在控制骨骼肌收缩方面起着至关重要的作用。NMJ的形成依赖于Agrin/Lrp4/MuSK/Dok-7信号通路。然而，Dok-7下游的信号仍然不完全清楚。在这里，我们使用磷酸化iTRAQ技术鉴定肌肉细胞中Dok-7的下游分子。我们发现了16个Agrin/ dok -7介导的丝氨酸/苏氨酸磷酸化蛋白，并验证了其中一个磷酸化蛋白JPH2在调节AChR聚类中的作用。我们的磷酸化蛋白质组学分析揭示了Agrin/Dok-7下游被忽视的信号网络，从而为理解神经肌肉疾病的发病机制和开发治疗方法提供了新的线索。
期刊介绍：
FEBS Letters is one of the world''s leading journals in molecular biology and is renowned both for its quality of content and speed of production. Bringing together the most important developments in the molecular biosciences, FEBS Letters provides an international forum for Minireviews, Research Letters and Hypotheses that merit urgent publication.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
