{"title":"View from the PEAKs: Insights from structural studies on the PEAK family of pseudokinases","authors":"Isabelle S. Lucet , Roger J. Daly","doi":"10.1016/j.sbi.2024.102932","DOIUrl":null,"url":null,"abstract":"<div><div>The PEAK family of pseudokinase scaffolds, comprising PEAK1 (originally termed SgK269), PEAK2 (SgK223, the human orthologue of rat Pragmin) and PEAK3 (C19orf35), have emerged as important regulators and integrators of cellular signaling and also play oncogenic roles in a variety of human cancers. These proteins undergo both homo- and heterotypic association that act to diversify signal output. Recently, structural and functional characterization of PEAK3 and its protein–protein interactions have shed light on PEAK signaling dynamics and the interdependency of PEAK family members, how PEAK dimerization regulates the binding of downstream effectors, and how 14-3-3 binding acts to regulate PEAK3 signal output. These important advances form the basis of this review.</div></div>","PeriodicalId":10887,"journal":{"name":"Current opinion in structural biology","volume":"89 ","pages":"Article 102932"},"PeriodicalIF":6.1000,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0959440X24001593/pdfft?md5=16d184d9d4e2e0ccff5015a5e5e67ebc&pid=1-s2.0-S0959440X24001593-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current opinion in structural biology","FirstCategoryId":"99","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0959440X24001593","RegionNum":2,"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
The PEAK family of pseudokinase scaffolds, comprising PEAK1 (originally termed SgK269), PEAK2 (SgK223, the human orthologue of rat Pragmin) and PEAK3 (C19orf35), have emerged as important regulators and integrators of cellular signaling and also play oncogenic roles in a variety of human cancers. These proteins undergo both homo- and heterotypic association that act to diversify signal output. Recently, structural and functional characterization of PEAK3 and its protein–protein interactions have shed light on PEAK signaling dynamics and the interdependency of PEAK family members, how PEAK dimerization regulates the binding of downstream effectors, and how 14-3-3 binding acts to regulate PEAK3 signal output. These important advances form the basis of this review.
期刊介绍：
Current Opinion in Structural Biology (COSB) aims to stimulate scientifically grounded, interdisciplinary, multi-scale debate and exchange of ideas. It contains polished, concise and timely reviews and opinions, with particular emphasis on those articles published in the past two years. In addition to describing recent trends, the authors are encouraged to give their subjective opinion of the topics discussed.
In COSB, we help the reader by providing in a systematic manner:
1. The views of experts on current advances in their field in a clear and readable form.
2. Evaluations of the most interesting papers, annotated by experts, from the great wealth of original publications.
[...]
The subject of Structural Biology is divided into twelve themed sections, each of which is reviewed once a year. Each issue contains two sections, and the amount of space devoted to each section is related to its importance.
-Folding and Binding-
Nucleic acids and their protein complexes-
Macromolecular Machines-
Theory and Simulation-
Sequences and Topology-
New constructs and expression of proteins-
Membranes-
Engineering and Design-
Carbohydrate-protein interactions and glycosylation-
Biophysical and molecular biological methods-
Multi-protein assemblies in signalling-
Catalysis and Regulation
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